chr1-108834974-G-T

Variant names:

• chr1-108834974-G-T
• NM_152763.5:c.1619C>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.1619C>A​(p.Pro540Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P540T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AKNAD1 NM_152763.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.84

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=0.10554129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKNAD1	NM_152763.5	c.1619C>A	p.Pro540Gln	missense_variant	Exon 8 of 16	ENST00000370001.8	NP_689976.2
AKNAD1	NR_049760.2	n.1958+2576C>A		intron_variant	Intron 8 of 13
LOC105378891	XR_007066273.1	n.294+638G>T		intron_variant	Intron 3 of 4
LOC105378891	XR_947687.3	n.269+638G>T		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKNAD1	ENST00000370001.8	c.1619C>A	p.Pro540Gln	missense_variant	Exon 8 of 16	1	NM_152763.5	ENSP00000359018.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1619C>A (p.P540Q) alteration is located in exon 8 (coding exon 7) of the AKNAD1 gene. This alteration results from a C to A substitution at nucleotide position 1619, causing the proline (P) at amino acid position 540 to be replaced by a glutamine (Q). 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	0.089
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.035
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0040	T;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.64	N;N
REVEL	Benign	0.035
Sift	Benign	0.052	T;D
Sift4G	Benign	0.19	T;T
Polyphen		0.0020	B;.
Vest4		0.17
MutPred		0.23		Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);
MVP		0.055
MPC		0.025
ClinPred		0.28	T
GERP RS		1.4
Varity_R		0.023
gMVP		0.098

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-109377596;