Variant chr16-21644354-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_005849.4(IGSF6):c.470C>T(p.Ala157Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,886 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

IGSF6
NM_005849.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.338

Variant links:

Genes affected

IGSF6 (HGNC:5953): (immunoglobulin superfamily member 6) Predicted to enable transmembrane signaling receptor activity. Predicted to be involved in cell surface receptor signaling pathway and immune response. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

IGSF6 links:

METTL9 (HGNC:24586): (methyltransferase 9, His-X-His N1(pi)-histidine) Enables protein-L-histidine N-pros-methyltransferase activity. Predicted to be involved in methylation. Is active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

METTL9 links:

LOC124903663 (HGNC:):

LOC124903663 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=0.047789335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IGSF6	NM_005849.4 linkuse as main transcript	c.470C>T	p.Ala157Val	missense_variant	3/6	ENST00000268389.6
METTL9	NM_016025.5 linkuse as main transcript	c.752-10873G>A		intron_variant		ENST00000358154.8
LOC124903663	XR_007065025.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF6	ENST00000268389.6 linkuse as main transcript	c.470C>T	p.Ala157Val	missense_variant	3/6	1	NM_005849.4	P1
METTL9	ENST00000358154.8 linkuse as main transcript	c.752-10873G>A		intron_variant		1	NM_016025.5	P3	Q9H1A3-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250864

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461694

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.2

DANN

Benign

0.96

DEOGEN2

Benign

0.030

T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.063

M_CAP

Benign

0.0064

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.96

L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.50

N;N

REVEL

Benign

0.028

Sift

Benign

0.81

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.19

B;.

Vest4

0.075

MutPred

0.29

Loss of loop (P = 0.0603);.;

MVP

0.072

MPC

0.20

ClinPred

0.052

GERP RS

2.5

Varity_R

0.030

gMVP

0.31

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over