chr9-38577258-C-T

Variant names:

• chr9-38577258-C-T
• NM_147195.4:c.2536G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2012822).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147195.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD18A	NM_147195.4	MANE Select	c.2536G>A	p.Ala846Thr	missense	Exon 14 of 16	NP_671728.2	Q8IVF6-1
	ANKRD18A	NM_001331100.2		c.2722G>A	p.Ala908Thr	missense	Exon 16 of 18	NP_001318029.1	A0A8V8TQR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD18A	ENST00000399703.6	TSL:1 MANE Select	c.2536G>A	p.Ala846Thr	missense	Exon 14 of 16	ENSP00000382610.4	Q8IVF6-1
	ANKRD18A	ENST00000602295.5	TSL:1	c.706G>A	p.Ala236Thr	missense	Exon 6 of 8	ENSP00000473463.1	R4GN29
	ANKRD18A	ENST00000703205.1		c.2722G>A	p.Ala908Thr	missense	Exon 16 of 18	ENSP00000515234.1	A0A8V8TQR3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		2.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.080	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
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr9-38577255;