9-38577258-C-T

Position:

• chr9-38577258-C-T

Variant summary

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

The NM_147195.4(ANKRD18A):​c.2536G>A​(p.Ala846Thr) 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. 12/21 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: ANKRD18A NM_147195.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.34

Genes affected

ANKRD18A (HGNC:23643): (ankyrin repeat domain 18A)

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=0.2012822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD18A	NM_147195.4	c.2536G>A	p.Ala846Thr	missense_variant	14/16	ENST00000399703.6	NP_671728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD18A	ENST00000399703.6	c.2536G>A	p.Ala846Thr	missense_variant	14/16	1	NM_147195.4	ENSP00000382610	A2
ANKRD18A	ENST00000602295.5	c.706G>A	p.Ala236Thr	missense_variant	6/8	1		ENSP00000473463
ANKRD18A	ENST00000703205.1	c.2722G>A	p.Ala908Thr	missense_variant	16/18			ENSP00000515234	P2
ANKRD18A	ENST00000703204.1	c.*1496G>A		3_prime_UTR_variant, NMD_transcript_variant	11/17			ENSP00000515233

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

May 23, 2023

The c.2536G>A (p.A846T) alteration is located in exon 14 (coding exon 14) of the ANKRD18A gene. This alteration results from a G to A substitution at nucleotide position 2536, causing the alanine (A) at amino acid position 846 to be replaced by a threonine (T). 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	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.9	.;M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.6	.;D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	.;D
Sift4G	Benign	0.080	T;T
Polyphen		0.92	.;P
Vest4		0.21
MutPred		0.080		.;Gain of methylation at K850 (P = 0.073);
MVP		0.22
MPC		0.20
ClinPred		0.95	D
GERP RS		1.5
Varity_R		0.15
gMVP		0.018

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr9-38577255;