9-38577090-C-A

Variant names:

• chr9-38577090-C-A
• rs180784545
• NM_147195.4:c.2704G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_147195.4(ANKRD18A):​c.2704G>T​(p.Val902Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V902M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD18A NM_147195.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024429947).

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.2704G>T	p.Val902Leu	missense	Exon 14 of 16	NP_671728.2	Q8IVF6-1
	ANKRD18A	NM_001331100.2		c.2890G>T	p.Val964Leu	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.2704G>T	p.Val902Leu	missense	Exon 14 of 16	ENSP00000382610.4	Q8IVF6-1
	ANKRD18A	ENST00000602295.5	TSL:1	c.874G>T	p.Val292Leu	missense	Exon 6 of 8	ENSP00000473463.1	R4GN29
	ANKRD18A	ENST00000703205.1		c.2890G>T	p.Val964Leu	missense	Exon 16 of 18	ENSP00000515234.1	A0A8V8TQR3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0060
DANN	Benign	0.10
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00032	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.1	N
PhyloP100		-0.60
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.0090
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.013
MutPred		0.26		Loss of methylation at K903 (P = 0.0415)
MVP		0.014
MPC		0.027
ClinPred		0.059	T
GERP RS		-1.2
Varity_R		0.044
gMVP		0.0078
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs180784545; hg19: chr9-38577087; COSMIC: COSV57632486;