NM_152763.5:c.2104C>A

Variant names:

• chr1-108823433-G-T
• rs1023388636
• NM_152763.5:c.2104C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152763.5(AKNAD1):​c.2104C>A​(p.His702Asn) 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. 15/21 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. H702Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AKNAD1 NM_152763.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.855

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07587314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKNAD1	NM_152763.5	c.2104C>A	p.His702Asn	missense_variant	Exon 13 of 16	ENST00000370001.8	NP_689976.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKNAD1	ENST00000370001.8	c.2104C>A	p.His702Asn	missense_variant	Exon 13 of 16	1	NM_152763.5	ENSP00000359018.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0063	T;.;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.076	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.078
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.66	T;T;T
Polyphen		0.82	P;.;.
Vest4		0.34
MutPred		0.26		Loss of helix (P = 0.0167);.;Loss of helix (P = 0.0167);
MVP		0.014
MPC		0.14
ClinPred		0.34	T
GERP RS		0.36
Varity_R		0.084
gMVP		0.035

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1023388636; hg19: chr1-109366055;