1-145872697-C-T

Variant names:

• chr1-145872697-C-T
• rs1653885825
• NM_144698.5:c.2072G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144698.5(ANKRD35):​c.2072G>A​(p.Arg691Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD35 NM_144698.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05

Genes affected

ANKRD35 (HGNC:26323): (ankyrin repeat domain 35)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36120218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD35	NM_144698.5	c.2072G>A	p.Arg691Gln	missense_variant	Exon 10 of 14	ENST00000355594.9	NP_653299.4
ANKRD35	NM_001280799.2	c.1802G>A	p.Arg601Gln	missense_variant	Exon 8 of 12		NP_001267728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD35	ENST00000355594.9	c.2072G>A	p.Arg691Gln	missense_variant	Exon 10 of 14	2	NM_144698.5	ENSP00000347802.4
ANKRD35	ENST00000544626.2	c.1802G>A	p.Arg601Gln	missense_variant	Exon 8 of 12	5		ENSP00000442671.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 96

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2072G>A (p.R691Q) alteration is located in exon 10 (coding exon 10) of the ANKRD35 gene. This alteration results from a G to A substitution at nucleotide position 2072, causing the arginine (R) at amino acid position 691 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	0.086
BayesDel_noAF	Uncertain	0.12
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.020	.;T
LIST_S2	Uncertain	0.88	.;D
MetaRNN	Benign	0.36	T;T
PROVEAN	Benign	-0.38	N;.
Sift	Uncertain	0.0050	D;.
Sift4G	Benign	0.080	T;T
Vest4		0.52
gMVP		0.65

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: rs1653885825; hg19: chr1-145562384;