dbSNP rs777496821: SAMD7:p.Met165Ile (chr3-169926757-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001304366.2(SAMD7):c.495G>A(p.Met165Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SAMD7
NM_001304366.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05747333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD7	NM_001304366.2 link	c.495G>A	p.Met165Ile	missense_variant	Exon 6 of 9	ENST00000335556.7	NP_001291295.1	Q7Z3H4
SAMD7	NM_182610.4 link	c.495G>A	p.Met165Ile	missense_variant	Exon 6 of 9		NP_872416.1	Q7Z3H4
SAMD7	NR_130713.2 link	n.974G>A		non_coding_transcript_exon_variant	Exon 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SAMD7	ENST00000335556.7 link	c.495G>A	p.Met165Ile	missense_variant	Exon 6 of 9	1	NM_001304366.2	ENSP00000334668.3	Q7Z3H4
SAMD7	ENST00000428432.6 link	c.495G>A	p.Met165Ile	missense_variant	Exon 6 of 9	1		ENSP00000391299.2	Q7Z3H4
SAMD7	ENST00000487910.1 link	n.*311G>A		non_coding_transcript_exon_variant	Exon 6 of 9	1		ENSP00000420460.1	F8WDF1
SAMD7	ENST00000487910.1 link	n.*311G>A		3_prime_UTR_variant	Exon 6 of 9	1		ENSP00000420460.1	F8WDF1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251416

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135894

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151972

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.8

DANN

Benign

0.51

DEOGEN2

Benign

0.0017

T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.46

.;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.057

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.89

N;N

REVEL

Benign

0.047

Sift

Benign

0.69

T;T

Sift4G

Benign

0.90

T;T

Polyphen

0.0010

B;B

Vest4

0.15

MutPred

0.37

Loss of disorder (P = 0.0384);Loss of disorder (P = 0.0384);

MVP

0.19

MPC

0.15

ClinPred

0.027

GERP RS

0.77

Varity_R

0.058

gMVP

0.074

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over