11-62517320-C-T

Variant names:

• chr11-62517320-C-T
• rs111551528
• NM_001620.3:c.17097G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001620.3(AHNAK):​c.17097G>A​(p.Glu5699Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00532 in 1,614,182 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (32 hom.)
• Consequence: AHNAK NM_001620.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.249
• Publications: 3 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 11-62517320-C-T is Benign according to our data. Variant chr11-62517320-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 718175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.249 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 32 AR gene

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.17097G>A	p.Glu5699Glu	synonymous	Exon 5 of 5	NP_001611.1	Q09666-1
	AHNAK	NM_001346445.2		c.17097G>A	p.Glu5699Glu	synonymous	Exon 5 of 5	NP_001333374.1	Q09666-1
	AHNAK	NM_001346446.2		c.17097G>A	p.Glu5699Glu	synonymous	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.17097G>A	p.Glu5699Glu	synonymous	Exon 5 of 5	ENSP00000367263.4	Q09666-1
	AHNAK	ENST00000257247.11	TSL:1	c.342+17683G>A		intron	N/A	ENSP00000257247.7	Q09666-2
	AHNAK	ENST00000530124.5	TSL:3	c.342+17683G>A		intron	N/A	ENSP00000433789.1	E9PJC6

Frequencies

GnomAD3 genomes AF: 0.00339 AC: 516 AN: 152192 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00558

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00401 AC: 1006 AN: 251044 AF XY: 0.00416

Gnomad AFR exome AF: 0.000924

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00656

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00531

Gnomad NFE exome AF: 0.00665

Gnomad OTH exome AF: 0.00490

GnomAD4 exome AF: 0.00552 AC: 8075 AN: 1461872 Hom.: 32 Cov.: 58 AF XY: 0.00544 AC XY: 3953 AN XY: 727234

African (AFR) AF: 0.00102 AC: 34 AN: 33480

American (AMR) AF: 0.000425 AC: 19 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00627 AC: 164 AN: 26136

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

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86258

European-Finnish (FIN) AF: 0.00569 AC: 304 AN: 53408

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00655 AC: 7283 AN: 1112004

Other (OTH) AF: 0.00401 AC: 242 AN: 60396

GnomAD4 genome AF: 0.00339 AC: 516 AN: 152310 Hom.: 1 Cov.: 32 AF XY: 0.00341 AC XY: 254 AN XY: 74468

African (AFR) AF: 0.000890 AC: 37 AN: 41568

American (AMR) AF: 0.000915 AC: 14 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00499 AC: 53 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00559 AC: 380 AN: 68036

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00388 Hom.: 0

Bravo AF: 0.00297

EpiCase AF: 0.00523

EpiControl AF: 0.00522

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.27
DANN	Benign	0.67
PhyloP100		-0.25
Mutation Taster		=100/0	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: rs111551528; hg19: chr11-62284792;