rs11231128

Variant names:

• chr11-62523247-A-G
• rs11231128
• NM_001620.3:c.11170T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.049 (319 hom., cov: 32)
  • Exomes 𝑓: 0.029 (777 hom.)
• Consequence: AHNAK NM_001620.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• Publications: 17 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AHNAK	NM_001620.3	c.11170T>C	p.Ser3724Pro	missense_variant	Exon 5 of 5	ENST00000378024.9	NP_001611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHNAK	ENST00000378024.9	c.11170T>C	p.Ser3724Pro	missense_variant	Exon 5 of 5	2	NM_001620.3	ENSP00000367263.4
AHNAK	ENST00000257247.11	c.342+11756T>C		intron_variant	Intron 4 of 5	1		ENSP00000257247.7
AHNAK	ENST00000530124.5	c.342+11756T>C		intron_variant	Intron 2 of 2	3		ENSP00000433789.1
AHNAK	ENST00000533365.5	c.342+11756T>C		intron_variant	Intron 4 of 4	5		ENSP00000433635.1

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7209 AN: 147254 Hom.: 314 Cov.: 32

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

GnomAD2 exomes AF: 0.0307 AC: 7703 AN: 251274 AF XY: 0.0301

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 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.: 83 AF XY: 0.0295 AC XY: 21457 AN XY: 727240

African (AFR) AF: 0.106 AC: 3555 AN: 33470

American (AMR) AF: 0.0178 AC: 797 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0394 AC: 1029 AN: 26134

East Asian (EAS) AF: 0.00874 AC: 347 AN: 39700

South Asian (SAS) AF: 0.0286 AC: 2467 AN: 86254

European-Finnish (FIN) AF: 0.0118 AC: 629 AN: 53416

Middle Eastern (MID) AF: 0.0707 AC: 408 AN: 5768

European-Non Finnish (NFE) AF: 0.0283 AC: 31461 AN: 1112006

Other (OTH) AF: 0.0360 AC: 2177 AN: 60396

GnomAD4 genome AF: 0.0492 AC: 7253 AN: 147372 Hom.: 319 Cov.: 32 AF XY: 0.0488 AC XY: 3512 AN XY: 71896

African (AFR) AF: 0.109 AC: 4337 AN: 39668

American (AMR) AF: 0.0346 AC: 514 AN: 14848

Ashkenazi Jewish (ASJ) AF: 0.0457 AC: 157 AN: 3432

East Asian (EAS) AF: 0.00958 AC: 47 AN: 4908

South Asian (SAS) AF: 0.0292 AC: 136 AN: 4662

European-Finnish (FIN) AF: 0.00976 AC: 98 AN: 10044

Middle Eastern (MID) AF: 0.0772 AC: 21 AN: 272

European-Non Finnish (NFE) AF: 0.0273 AC: 1822 AN: 66628

Other (OTH) AF: 0.0504 AC: 103 AN: 2044

Alfa AF: 0.0333 Hom.: 561

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	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.22
DEOGEN2	Benign	0.076	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.0	N
PhyloP100		2.9
PrimateAI	Benign	0.27	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.012
MPC		0.028
ClinPred		0.0058	T
GERP RS		4.4
Varity_R		0.056
gMVP		0.019
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11231128; hg19: chr11-62290719; COSMIC: COSV107227706;