chr5-75068652-T-C

Position:

• chr5-75068652-T-C

Variant summary

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

The NM_001372053.1(ANKRD31):​c.5660A>G​(p.Glu1887Gly) 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. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD31 NM_001372053.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.764

Genes affected

ANKRD31 (HGNC:26853): (ankyrin repeat domain 31) This gene encodes a protein containing multiple ankyrin repeats. Ankyrin domains function in protein-protein interactions in a variety of cellular processes. Mutations in this gene are associated with a Rett syndrome (RTT)-like phenotype. [provided by RefSeq, Apr 2017]

ANKRD31 (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=0.11066741).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD31	NM_001372053.1	c.5660A>G	p.Glu1887Gly	missense_variant	26/26	ENST00000506364.6	NP_001358982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD31	ENST00000506364.6	c.5660A>G	p.Glu1887Gly	missense_variant	26/26	5	NM_001372053.1	ENSP00000427262.2

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 21, 2024

The c.5489A>G (p.E1830G) alteration is located in exon 25 (coding exon 25) of the ANKRD31 gene. This alteration results from a A to G substitution at nucleotide position 5489, causing the glutamic acid (E) at amino acid position 1830 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0057	.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.2	.;N
REVEL	Benign	0.091
Sift	Benign	0.11	.;T
Sift4G	Pathogenic	0.0	D;D
Vest4		0.18
MutPred		0.18		.;Loss of solvent accessibility (P = 0.0224);
MVP		0.27
ClinPred		0.24	T
GERP RS		4.8
Varity_R		0.097
gMVP		0.042

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr5-74364477;