Genetic Variant SAMD7:p.Arg92Gln (chr3-169925121-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001304366.2(SAMD7):c.275G>A(p.Arg92Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000922 in 1,605,844 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R92W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

SAMD7
NM_001304366.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

Publications

0 publications found

Variant links:

Genes affected

SAMD7 (HGNC:25394): (sterile alpha motif domain containing 7) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SAMD7 Gene-Disease associations (from GenCC):

macular dystrophy with or without cone dysfunction
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics

SAMD7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18661246).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304366.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD7	NM_001304366.2	MANE Select	c.275G>A	p.Arg92Gln	missense	Exon 5 of 9	NP_001291295.1	Q7Z3H4
SAMD7	NM_182610.4		c.275G>A	p.Arg92Gln	missense	Exon 5 of 9	NP_872416.1	Q7Z3H4
SAMD7	NR_130713.2		n.641G>A		non_coding_transcript_exon	Exon 5 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD7	ENST00000335556.7	TSL:1 MANE Select	c.275G>A	p.Arg92Gln	missense	Exon 5 of 9	ENSP00000334668.3	Q7Z3H4
SAMD7	ENST00000428432.6	TSL:1	c.275G>A	p.Arg92Gln	missense	Exon 5 of 9	ENSP00000391299.2	Q7Z3H4
SAMD7	ENST00000487910.1	TSL:1	n.275G>A		non_coding_transcript_exon	Exon 4 of 9	ENSP00000420460.1	F8WDF1

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

151818

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:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000125

AC:

AN:

247524

AF XY:

0.000149

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:

0.000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000928

AC:

135

AN:

1454026

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

723006

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33268

American (AMR)

AF:

0.00

AC:

AN:

43930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25972

East Asian (EAS)

AF:

0.00

AC:

AN:

39440

South Asian (SAS)

AF:

0.000437

AC:

AN:

84752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53312

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000858

AC:

AN:

1107540

Other (OTH)

AF:

0.0000499

AC:

AN:

60064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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:

0.0000856

AC:

AN:

151818

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41336

American (AMR)

AF:

0.00

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00104

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67958

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.000180

Hom.:

Bravo

AF:

0.0000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.80

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.5

PhyloP100

3.4

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.3

REVEL

Benign

0.10

Sift

Uncertain

0.023

Sift4G

Uncertain

0.055

Polyphen

0.99

Vest4

0.53

MVP

0.52

MPC

0.35

ClinPred

0.54

GERP RS

4.3

Varity_R

0.098

gMVP

0.27

Mutation Taster

=94/6

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

Computational scores

Splicing

Publications

Other links and lift over