Variant 6-107707990-G-A 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_198081.5(SCML4):c.995C>T(p.Ala332Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,551,000 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 23 hom. )

Consequence

SCML4
NM_198081.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00700

Variant links:

Genes affected

SCML4 (HGNC:21397): (Scm polycomb group protein like 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SCML4 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=0.003089875).

BP6

Variant 6-107707990-G-A is Benign according to our data. Variant chr6-107707990-G-A is described in ClinVar as [Benign]. Clinvar id is 787307.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCML4	NM_198081.5 linkuse as main transcript	c.995C>T	p.Ala332Val	missense_variant	7/8	ENST00000369020.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCML4	ENST00000369020.8 linkuse as main transcript	c.995C>T	p.Ala332Val	missense_variant	7/8	5	NM_198081.5	P1	Q8N228-1
SCML4	ENST00000369025.6 linkuse as main transcript	c.269C>T	p.Ala90Val	missense_variant	3/4	1
SCML4	ENST00000369022.6 linkuse as main transcript	c.821C>T	p.Ala274Val	missense_variant	6/7	2			Q8N228-2

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

218

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00322

AC:

500

AN:

155232

Hom.:

AF XY:

0.00396

AC XY:

326

AN XY:

82348

show subpopulations

Gnomad AFR exome

AF:

0.00238

Gnomad AMR exome

AF:

0.000811

Gnomad ASJ exome

AF:

0.000944

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0159

Gnomad FIN exome

AF:

0.000683

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00158

AC:

2208

AN:

1398782

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

1392

AN XY:

689946

show subpopulations

Gnomad4 AFR exome

AF:

0.00168

Gnomad4 AMR exome

AF:

0.000672

Gnomad4 ASJ exome

AF:

0.000755

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.0150

Gnomad4 FIN exome

AF:

0.000925

Gnomad4 NFE exome

AF:

0.000663

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00143

AC:

218

AN:

152218

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.000970

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00131

Hom.:

Bravo

AF:

0.00127

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000943

AC:

ExAC

AF:

0.00476

AC:

129

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.9

DANN

Benign

0.47

DEOGEN2

Benign

0.0056

.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.37

T;T;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

.;.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.60

N;N;N

REVEL

Benign

0.014

Sift

Benign

0.45

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.0010

.;.;B

Vest4

0.039

MVP

0.088

MPC

0.15

ClinPred

0.0011

GERP RS

2.8

Varity_R

0.021

gMVP

0.41

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