Variant 14-77378338-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001010860.4(SAMD15):c.920G>A(p.Arg307Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000807 in 1,612,474 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00068 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 0 hom. )

Consequence

SAMD15
NM_001010860.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.383

Variant links:

Genes affected

SAMD15 (HGNC:18631): (sterile alpha motif domain containing 15)

SAMD15 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=0.0066140294).

BP6

Variant 14-77378338-G-A is Benign according to our data. Variant chr14-77378338-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2357718.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMD15	NM_001010860.4 linkuse as main transcript	c.920G>A	p.Arg307Gln	missense_variant	1/3	ENST00000216471.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMD15	ENST00000216471.5 linkuse as main transcript	c.920G>A	p.Arg307Gln	missense_variant	1/3	2	NM_001010860.4	P1	Q9P1V8-1
SAMD15	ENST00000533095.2 linkuse as main transcript	c.-70+1598G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000684

AC:

104

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000594

AC:

148

AN:

249250

Hom.:

AF XY:

0.000541

AC XY:

AN XY:

134816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000265

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00107

Gnomad NFE exome

AF:

0.000991

Gnomad OTH exome

AF:

0.000497

GnomAD4 exome

AF:

0.000820

AC:

1198

AN:

1460232

Hom.:

Cov.:

AF XY:

0.000801

AC XY:

582

AN XY:

726474

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000249

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00109

Gnomad4 NFE exome

AF:

0.000961

Gnomad4 OTH exome

AF:

0.000846

GnomAD4 genome

AF:

0.000683

AC:

104

AN:

152242

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000940

Hom.:

Bravo

AF:

0.000480

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000593

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.000474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

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

0.063

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.79

Cadd

Benign

0.74

Dann

Benign

0.60

DEOGEN2

Benign

0.0019

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00053

LIST_S2

Benign

0.39

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0066

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.17

PROVEAN

Benign

0.72

REVEL

Benign

0.015

Sift

Benign

1.0

Sift4G

Benign

0.53

Polyphen

0.0010

Vest4

0.088

MVP

0.040

MPC

0.084

ClinPred

0.0089

GERP RS

-1.0

Varity_R

0.021

gMVP

0.013

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