rs375729380

Variant names:

• chr11-62517284-C-A
• rs375729380
• NM_001620.3:c.17133G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001620.3(AHNAK):​c.17133G>T​(p.Lys5711Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: AHNAK NM_001620.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.233
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15181693).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001620.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHNAK	NM_001620.3	MANE Select	c.17133G>T	p.Lys5711Asn	missense	Exon 5 of 5	NP_001611.1	Q09666-1
	AHNAK	NM_001346445.2		c.17133G>T	p.Lys5711Asn	missense	Exon 5 of 5	NP_001333374.1	Q09666-1
	AHNAK	NM_001346446.2		c.17133G>T	p.Lys5711Asn	missense	Exon 5 of 5	NP_001333375.1	Q09666-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHNAK	ENST00000378024.9	TSL:2 MANE Select	c.17133G>T	p.Lys5711Asn	missense	Exon 5 of 5	ENSP00000367263.4	Q09666-1
	AHNAK	ENST00000257247.11	TSL:1	c.342+17719G>T		intron	N/A	ENSP00000257247.7	Q09666-2
	AHNAK	ENST00000530124.5	TSL:3	c.342+17719G>T		intron	N/A	ENSP00000433789.1	E9PJC6

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250842 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000432

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461844 Hom.: 0 Cov.: 60 AF XY: 0.00000688 AC XY: 5 AN XY: 727224

African (AFR) AF: 0.000388 AC: 13 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.0000497 AC: 3 AN: 60394

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74428

African (AFR) AF: 0.000313 AC: 13 AN: 41534

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000127 Hom.: 0

Bravo AF: 0.0000869

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		-0.23
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.16
Sift	Benign	0.11	T
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.30
MutPred		0.27		Loss of methylation at K5711 (P = 0.0098)
MVP		0.048
MPC		0.22
ClinPred		0.97	D
GERP RS		-2.1
Varity_R		0.16
gMVP		0.25
Mutation Taster		=81/19	polymorphism

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: rs375729380; hg19: chr11-62284756;