1-108827229-C-A

Variant names:

• chr1-108827229-C-A
• rs775377275
• NM_152763.5:c.1912G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152763.5(AKNAD1):​c.1912G>T​(p.Ala638Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A638T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AKNAD1 NM_152763.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

Genes affected

AKNAD1 (HGNC:28398): (AKNA domain containing 1) This gene encodes a protein which contains a domain found in an AT-hook-containing transcription factor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

LOC105378891 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056111753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKNAD1	NM_152763.5	c.1912G>T	p.Ala638Ser	missense_variant	Exon 11 of 16	ENST00000370001.8	NP_689976.2
AKNAD1	NR_049760.2	n.2124G>T		non_coding_transcript_exon_variant	Exon 10 of 14
LOC105378891	XR_007066273.1	n.147+3511C>A		intron_variant	Intron 2 of 4
LOC105378891	XR_947687.3	n.122+3511C>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKNAD1	ENST00000370001.8	c.1912G>T	p.Ala638Ser	missense_variant	Exon 11 of 16	1	NM_152763.5	ENSP00000359018.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0036	T;.;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.46	T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	L;.;L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.87	N;N;N
REVEL	Benign	0.017
Sift	Benign	0.037	D;D;D
Sift4G	Benign	0.34	T;T;T
Polyphen		0.44	B;.;.
Vest4		0.056
MutPred		0.15		Gain of disorder (P = 0.0205);.;Gain of disorder (P = 0.0205);
MVP		0.014
MPC		0.026
ClinPred		0.13	T
GERP RS		0.99
Varity_R		0.045
gMVP		0.015

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

LitVar

Other links and lift over

dbSNP: rs775377275; hg19: chr1-109369851;