3-169926861-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001304366.2(SAMD7):c.599G>A(p.Ser200Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,918 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SAMD7
NM_001304366.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.825

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013253659).

BP6

Variant 3-169926861-G-A is Benign according to our data. Variant chr3-169926861-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3791887.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD7	NM_001304366.2 link	c.599G>A	p.Ser200Asn	missense_variant	Exon 6 of 9	ENST00000335556.7	NP_001291295.1	Q7Z3H4
SAMD7	NM_182610.4 link	c.599G>A	p.Ser200Asn	missense_variant	Exon 6 of 9		NP_872416.1	Q7Z3H4
SAMD7	NR_130713.2 link	n.1078G>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.599G>A	p.Ser200Asn	missense_variant	Exon 6 of 9	1	NM_001304366.2	ENSP00000334668.3	Q7Z3H4
SAMD7	ENST00000428432.6 link	c.599G>A	p.Ser200Asn	missense_variant	Exon 6 of 9	1		ENSP00000391299.2	Q7Z3H4
SAMD7	ENST00000487910.1 link	n.*415G>A		non_coding_transcript_exon_variant	Exon 6 of 9	1		ENSP00000420460.1	F8WDF1
SAMD7	ENST00000487910.1 link	n.*415G>A		3_prime_UTR_variant	Exon 6 of 9	1		ENSP00000420460.1	F8WDF1

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000653

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:

0.0000358

AC:

AN:

251244

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.000555

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000178

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000651

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

Alfa

AF:

0.0000216

Hom.:

Bravo

AF:

0.000238

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 20, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.4

DANN

Benign

0.39

DEOGEN2

Benign

0.0027

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.45

.;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.92

N;N

REVEL

Benign

0.051

Sift

Benign

0.48

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.0010

B;B

Vest4

0.046

MVP

0.21

MPC

0.13

ClinPred

0.021

GERP RS

-1.1

Varity_R

0.051

gMVP

0.055

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over