Variant 19-43612556-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001145641.2(SRRM5):c.435A>G(p.Ile145Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 1,551,510 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00065 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 4 hom. )

Consequence

SRRM5
NM_001145641.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0110

Variant links:

Genes affected

SRRM5 (HGNC:37248): (serine/arginine repetitive matrix 5)

SRRM5 links:

ZNF428 (HGNC:20804): (zinc finger protein 428) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZNF428 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014071614).

BP6

Variant 19-43612556-A-G is Benign according to our data. Variant chr19-43612556-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2350665.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRRM5	NM_001145641.2 link	c.435A>G	p.Ile145Met	missense_variant	1/1	ENST00000417606.3	NP_001139113.1	B3KS81Q4G0Z0
ZNF428	NM_182498.4 link	c.76+1673T>C		intron_variant		ENST00000300811.8	NP_872304.2	Q96B54I6L9C8
ZNF428	XM_047438168.1 link	c.76+1673T>C		intron_variant			XP_047294124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SRRM5	ENST00000417606.3 link	c.435A>G	p.Ile145Met	missense_variant	1/1	6	NM_001145641.2	ENSP00000414512.1	B3KS81
ZNF428	ENST00000300811.8 link	c.76+1673T>C		intron_variant		1	NM_182498.4	ENSP00000300811.2	Q96B54
SRRM5	ENST00000607544.1 link	c.435A>G	p.Ile145Met	missense_variant	3/3	2		ENSP00000476253.1	B3KS81
ZNF428	ENST00000598676.1 link	c.76+1673T>C		intron_variant		5		ENSP00000469484.1	M0QXZ5

Frequencies

GnomAD3 genomes

AF:

0.000651

AC:

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000610

AC:

AN:

153974

Hom.:

AF XY:

0.000746

AC XY:

AN XY:

81718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000729

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000439

Gnomad FIN exome

AF:

0.0000656

Gnomad NFE exome

AF:

0.000989

Gnomad OTH exome

AF:

0.00138

GnomAD4 exome

AF:

0.000698

AC:

977

AN:

1399388

Hom.:

Cov.:

AF XY:

0.000719

AC XY:

496

AN XY:

690202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.000616

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000404

Gnomad4 FIN exome

AF:

0.0000406

Gnomad4 NFE exome

AF:

0.000824

Gnomad4 OTH exome

AF:

0.000517

GnomAD4 genome

AF:

0.000651

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000686

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000754

Hom.:

Bravo

AF:

0.000703

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.000153

AC:

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

Jun 10, 2022

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

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.9

DANN

Benign

0.93

DEOGEN2

Benign

0.0011

T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.32

.;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.38

.;N

REVEL

Benign

0.020

Sift

Benign

0.043

.;D

Sift4G

Benign

0.11

T;T

Polyphen

0.025

B;B

Vest4

0.034

MVP

0.014

MPC

0.014

ClinPred

0.026

GERP RS

-0.41

Varity_R

0.081

gMVP

0.016

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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