22-29060720-C-A

Position:

• chr22-29060720-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015370.2(C22orf31):​c.127G>T​(p.Ala43Ser) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: C22orf31 NM_015370.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.115

Genes affected

C22orf31 (HGNC:26931): (chromosome 22 open reading frame 31)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04862067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C22orf31	NM_015370.2	c.127G>T	p.Ala43Ser	missense_variant	2/3	ENST00000216071.5	NP_056185.1
C22orf31	NM_001386866.1	c.4G>T	p.Ala2Ser	missense_variant	2/3		NP_001373795.1
C22orf31	XM_017028741.2	c.4G>T	p.Ala2Ser	missense_variant	2/3		XP_016884230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C22orf31	ENST00000216071.5	c.127G>T	p.Ala43Ser	missense_variant	2/3	1	NM_015370.2	ENSP00000216071.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Jan 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.8
DANN	Benign	0.90
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.033
Sift	Benign	0.31	T
Sift4G	Benign	0.67	T
Polyphen		0.12	B
Vest4		0.088
MutPred		0.32		Loss of helix (P = 0.0237);
MVP		0.088
MPC		0.056
ClinPred		0.099	T
GERP RS		1.4
Varity_R		0.063
gMVP		0.051

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: rs2037381966; hg19: chr22-29456708;