Variant chr11-62523247-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001620.3(AHNAK):c.11170T>C(p.Ser3724Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 1,609,238 control chromosomes in the GnomAD database, including 1,096 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.049 ( 319 hom., cov: 32)

Exomes 𝑓: 0.029 ( 777 hom. )

Consequence

AHNAK
NM_001620.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90

Variant links:

Genes affected

AHNAK (HGNC:347): (AHNAK nucleoprotein) The protein encoded by this gene is a large (700 kDa) structural scaffold protein consisting of a central domain with 128 aa repeats. The encoded protein may play a role in such diverse processes as blood-brain barrier formation, cell structure and migration, cardiac calcium channel regulation, and tumor metastasis. A much shorter variant encoding a 17 kDa isoform exists for this gene, and the shorter isoform initiates a feedback loop that regulates alternative splicing of this gene. [provided by RefSeq, Oct 2016]

AHNAK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014526248).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHNAK	NM_001620.3 linkuse as main transcript	c.11170T>C	p.Ser3724Pro	missense_variant	5/5	ENST00000378024.9	NP_001611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHNAK	ENST00000378024.9 linkuse as main transcript	c.11170T>C	p.Ser3724Pro	missense_variant	5/5	2	NM_001620.3	ENSP00000367263		Q09666-1
AHNAK	ENST00000257247.11 linkuse as main transcript	c.342+11756T>C		intron_variant		1		ENSP00000257247	P1	Q09666-2
AHNAK	ENST00000530124.5 linkuse as main transcript	c.342+11756T>C		intron_variant		3		ENSP00000433789
AHNAK	ENST00000533365.5 linkuse as main transcript	c.342+11756T>C		intron_variant		5		ENSP00000433635

Frequencies

GnomAD3 genomes

AF:

0.0490

AC:

7209

AN:

147254

Hom.:

314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.0457

Gnomad EAS

AF:

0.00976

Gnomad SAS

AF:

0.0293

Gnomad FIN

AF:

0.00976

Gnomad MID

AF:

0.0719

Gnomad NFE

AF:

0.0273

Gnomad OTH

AF:

0.0460

GnomAD3 exomes

AF:

0.0307

AC:

7703

AN:

251274

Hom.:

196

AF XY:

0.0301

AC XY:

4086

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.0163

Gnomad ASJ exome

AF:

0.0395

Gnomad EAS exome

AF:

0.0119

Gnomad SAS exome

AF:

0.0286

Gnomad FIN exome

AF:

0.0100

Gnomad NFE exome

AF:

0.0309

Gnomad OTH exome

AF:

0.0339

GnomAD4 exome

AF:

0.0293

AC:

42870

AN:

1461866

Hom.:

777

Cov.:

AF XY:

0.0295

AC XY:

21457

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.0178

Gnomad4 ASJ exome

AF:

0.0394

Gnomad4 EAS exome

AF:

0.00874

Gnomad4 SAS exome

AF:

0.0286

Gnomad4 FIN exome

AF:

0.0118

Gnomad4 NFE exome

AF:

0.0283

Gnomad4 OTH exome

AF:

0.0360

GnomAD4 genome

AF:

0.0492

AC:

7253

AN:

147372

Hom.:

319

Cov.:

AF XY:

0.0488

AC XY:

3512

AN XY:

71896

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.0346

Gnomad4 ASJ

AF:

0.0457

Gnomad4 EAS

AF:

0.00958

Gnomad4 SAS

AF:

0.0292

Gnomad4 FIN

AF:

0.00976

Gnomad4 NFE

AF:

0.0273

Gnomad4 OTH

AF:

0.0504

Alfa

AF:

0.0328

Hom.:

293

Bravo

AF:

0.0517

TwinsUK

AF:

0.0275

AC:

102

ALSPAC

AF:

0.0283

AC:

109

ESP6500AA

AF:

0.0972

AC:

428

ESP6500EA

AF:

0.0258

AC:

222

ExAC

AF:

0.0345

AC:

4195

Asia WGS

AF:

0.0370

AC:

127

AN:

3478

EpiCase

AF:

0.0305

EpiControl

AF:

0.0321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.22

DEOGEN2

Benign

0.076

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.0

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Benign

0.27

PROVEAN

Benign

2.6

REVEL

Benign

0.21

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.012

MPC

0.028

ClinPred

0.0058

GERP RS

4.4

Varity_R

0.056

gMVP

0.019

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