rs894106435

Variant names:

• chr18-5145603-G-C
• rs894106435
• NM_001145194.2:c.169C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-5145603-G-C
• chr18-5145603-G-T

Variant summary

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

The NM_001145194.2(AKAIN1):​c.169C>G​(p.Leu57Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000967 in 1,551,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: AKAIN1 NM_001145194.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10

Genes affected

AKAIN1 (HGNC:28285): (A-kinase anchor inhibitor 1) Enables protein kinase A binding activity. Involved in protein localization. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10343847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAIN1	NM_001145194.2	c.169C>G	p.Leu57Val	missense_variant	Exon 2 of 2	ENST00000434239.4	NP_001138666.1
AKAIN1	NM_001330553.2	c.190C>G	p.Leu64Val	missense_variant	Exon 2 of 2		NP_001317482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAIN1	ENST00000434239.4	c.169C>G	p.Leu57Val	missense_variant	Exon 2 of 2	2	NM_001145194.2	ENSP00000399075.3
AKAIN1	ENST00000580650.1	c.190C>G	p.Leu64Val	missense_variant	Exon 2 of 2	3		ENSP00000462259.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000779 AC: 12 AN: 154038 AF XY: 0.0000856

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000486

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: 0.0000100 AC: 14 AN: 1399318 Hom.: 0 Cov.: 30 AF XY: 0.0000116 AC XY: 8 AN XY: 690174

African (AFR) AF: 0.00 AC: 0 AN: 31586

American (AMR) AF: 0.000364 AC: 13 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078920

Other (OTH) AF: 0.00 AC: 0 AN: 57994

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 26, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.169C>G (p.L57V) alteration is located in exon 2 (coding exon 2) of the AKAIN1 gene. This alteration results from a C to G substitution at nucleotide position 169, causing the leucine (L) at amino acid position 57 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.051	.;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		3.1
PROVEAN	Benign	-1.8	.;N
REVEL	Benign	0.048
Sift	Benign	0.084	.;T
Sift4G	Uncertain	0.059	T;T
Polyphen		0.93	.;P
Vest4		0.12
MutPred		0.28		.;Gain of sheet (P = 0.0221);
MVP		0.092
ClinPred		0.16	T
GERP RS		4.8
Varity_R		0.13
gMVP		0.042
Mutation Taster		=90/10	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

Publications

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Other links and lift over

dbSNP: rs894106435; hg19: chr18-5145602;