rs111551528

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-62517320-C-A
• chr11-62517320-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001620.3(AHNAK):​c.17097G>T​(p.Glu5699Asp) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E5699E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHNAK NM_001620.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16159678).

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>T	p.Glu5699Asp	missense	Exon 5 of 5	NP_001611.1	Q09666-1
	AHNAK	NM_001346445.2		c.17097G>T	p.Glu5699Asp	missense	Exon 5 of 5	NP_001333374.1	Q09666-1
	AHNAK	NM_001346446.2		c.17097G>T	p.Glu5699Asp	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.17097G>T	p.Glu5699Asp	missense	Exon 5 of 5	ENSP00000367263.4	Q09666-1
	AHNAK	ENST00000257247.11	TSL:1	c.342+17683G>T		intron	N/A	ENSP00000257247.7	Q09666-2
	AHNAK	ENST00000530124.5	TSL:3	c.342+17683G>T		intron	N/A	ENSP00000433789.1	E9PJC6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.25
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.089
Sift	Benign	0.27	T
Sift4G	Uncertain	0.015	D
Polyphen		0.98	D
Vest4		0.092
MutPred		0.13		Gain of MoRF binding (P = 0.2547)
MVP		0.030
MPC		0.047
ClinPred		0.68	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.12
gMVP		0.076
Mutation Taster		=96/4	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;