1-108827229-C-G

Variant names:

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

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>C​(p.Ala638Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,842 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A638T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• 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=0.052082986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKNAD1	NM_152763.5	c.1912G>C	p.Ala638Pro	missense_variant	Exon 11 of 16	ENST00000370001.8	NP_689976.2
AKNAD1	NR_049760.2	n.2124G>C		non_coding_transcript_exon_variant	Exon 10 of 14
LOC105378891	XR_007066273.1	n.147+3511C>G		intron_variant	Intron 2 of 4
LOC105378891	XR_947687.3	n.122+3511C>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKNAD1	ENST00000370001.8	c.1912G>C	p.Ala638Pro	missense_variant	Exon 11 of 16	1	NM_152763.5	ENSP00000359018.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459842 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.4
DANN	Benign	0.96
DEOGEN2	Benign	0.0043	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.50	T;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.97	L;.;L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.028
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.21	T;D;T
Polyphen		0.011	B;.;.
Vest4		0.074
MutPred		0.17		Gain of disorder (P = 0.0287);.;Gain of disorder (P = 0.0287);
MVP		0.040
MPC		0.031
ClinPred		0.090	T
GERP RS		0.99
Varity_R		0.099
gMVP		0.041

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-109369851;