dbSNP rs760713904: ANKRD42:p.Thr16Ser (chr11-83194717-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001300975.2(ANKRD42):c.47C>G(p.Thr16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T16I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANKRD42
NM_001300975.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.858

Variant links:

Genes affected

ANKRD42 (HGNC:26752): (ankyrin repeat domain 42) Predicted to enable NF-kappaB binding activity. Predicted to act upstream of or within positive regulation of NF-kappaB transcription factor activity and positive regulation of cytokine production involved in inflammatory response. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD42 links:

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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=0.041656673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD42	NM_001300975.2 link	c.47C>G	p.Thr16Ser	missense_variant	Exon 1 of 11	ENST00000533342.6	NP_001287904.1	Q8N9B4E9PIL2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD42	ENST00000533342.6 link	c.47C>G	p.Thr16Ser	missense_variant	Exon 1 of 11	1	NM_001300975.2	ENSP00000435790.1		E9PIL2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000848

AC:

AN:

235924

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127824

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:

0.0000703

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000208

AC:

AN:

1443298

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716672

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:

0.0000356

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.0043

.;.;.;.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.52

T;T;T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.042

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.;.;L;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.71

N;N;N;N;N;N

REVEL

Benign

0.024

Sift

Pathogenic

0.0

D;T;D;T;T;T

Sift4G

Benign

0.36

T;T;T;T;T;T

Polyphen

0.0010

B;.;.;.;B;B

Vest4

0.086

MutPred

0.27

Loss of glycosylation at T16 (P = 0.0547);Loss of glycosylation at T16 (P = 0.0547);Loss of glycosylation at T16 (P = 0.0547);Loss of glycosylation at T16 (P = 0.0547);Loss of glycosylation at T16 (P = 0.0547);Loss of glycosylation at T16 (P = 0.0547);

MVP

0.37

MPC

0.12

ClinPred

0.23

GERP RS

0.37

Varity_R

0.088

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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