Variant 2-241073361-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001080437.3(SNED1):c.3913G>A(p.Gly1305Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,566,742 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

SNED1
NM_001080437.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

Variant links:

Genes affected

SNED1 (HGNC:24696): (sushi, nidogen and EGF like domains 1) Predicted to enable Notch binding activity. Predicted to be involved in cell-matrix adhesion. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SNED1 links:

SNED1 (HGNC:):

SNED1 links:

MTERF4 (HGNC:28785): (mitochondrial transcription termination factor 4) Enables rRNA binding activity. Predicted to be involved in rRNA processing and regulation of transcription, DNA-templated. Predicted to act upstream of or within several processes, including mitochondrial transcription; protein targeting to mitochondrion; and ribosome assembly. Located in cytosol and mitochondrion. Part of mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

MTERF4 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=0.0059509873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNED1	NM_001080437.3 linkuse as main transcript	c.3913G>A	p.Gly1305Arg	missense_variant	27/32	ENST00000310397.13	NP_001073906.1	Q8TER0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNED1	ENST00000310397.13 linkuse as main transcript	c.3913G>A	p.Gly1305Arg	missense_variant	27/32	5	NM_001080437.3	ENSP00000308893.8		Q8TER0-1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000318

AC:

AN:

172774

Hom.:

AF XY:

0.000336

AC XY:

AN XY:

92284

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00447

Gnomad EAS exome

AF:

0.0000823

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000140

Gnomad OTH exome

AF:

0.000421

GnomAD4 exome

AF:

0.000165

AC:

234

AN:

1414396

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

118

AN XY:

699156

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00447

Gnomad4 EAS exome

AF:

0.0000271

Gnomad4 SAS exome

AF:

0.0000250

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000781

Gnomad4 OTH exome

AF:

0.000426

GnomAD4 genome

AF:

0.000184

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000461

Hom.:

Bravo

AF:

0.000166

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000156

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 25, 2022

The c.3913G>A (p.G1305R) alteration is located in exon 27 (coding exon 27) of the SNED1 gene. This alteration results from a G to A substitution at nucleotide position 3913, causing the glycine (G) at amino acid position 1305 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.018

.;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.28

T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.16

Sift

Benign

0.060

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.015

B;P

Vest4

0.082

MutPred

0.17

Loss of methylation at K1302 (P = 0.1365);Loss of methylation at K1302 (P = 0.1365);

MVP

0.23

MPC

0.51

ClinPred

0.030

GERP RS

3.7

Varity_R

0.039

gMVP

0.25

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