rs754153159

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The ENST00000646673.2(SAMHD1):c.1258A>T(p.Thr420Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,611,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

SAMHD1
ENST00000646673.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1O:1

Conservation

PhyloP100: 2.45

Publications

0 publications found

Variant links:

Genes affected

SAMHD1 (HGNC:15925): (SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1) This gene may play a role in regulation of the innate immune response. The encoded protein is upregulated in response to viral infection and may be involved in mediation of tumor necrosis factor-alpha proinflammatory responses. Mutations in this gene have been associated with Aicardi-Goutieres syndrome. [provided by RefSeq, Mar 2010]

SAMHD1 Gene-Disease associations (from GenCC):

Aicardi-Goutieres syndrome 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
Moyamoya disease
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
Aicardi-Goutieres syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial chilblain lupus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
chilblain lupus 2
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
chilblain lupus
Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

SAMHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.266959).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000646673.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SAMHD1	NM_015474.4	MANE Select	c.1258A>T	p.Thr420Ser	missense	Exon 11 of 16	NP_056289.2
SAMHD1	NM_001363729.2		c.1258A>T	p.Thr420Ser	missense	Exon 11 of 15	NP_001350658.1
SAMHD1	NM_001363733.2		c.1258A>T	p.Thr420Ser	missense	Exon 11 of 16	NP_001350662.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SAMHD1	ENST00000646673.2	MANE Select	c.1258A>T	p.Thr420Ser	missense	Exon 11 of 16	ENSP00000493536.2
SAMHD1	ENST00000262878.5	TSL:1	c.1258A>T	p.Thr420Ser	missense	Exon 11 of 15	ENSP00000262878.5
SAMHD1	ENST00000643918.1		c.1258A>T	p.Thr420Ser	missense	Exon 11 of 16	ENSP00000493928.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251116

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1459012

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726064

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000423

AC:

AN:

1109872

Other (OTH)

AF:

0.0000166

AC:

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Aicardi-Goutieres syndrome 5 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.28

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.27

MetaSVM

Uncertain

0.038

MutationAssessor

Benign

1.8

PhyloP100

2.5

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.30

Sift

Benign

0.17

Sift4G

Benign

0.23

Polyphen

0.038

Vest4

0.28

MutPred

0.39

Loss of helix (P = 0.0167)

MVP

0.90

MPC

0.46

ClinPred

0.26

GERP RS

2.8

Varity_R

0.34

gMVP

0.52

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over