NM_020187.3:c.29C>T

Variant names:

• chr3-129279761-C-T
• rs1313109323
• NM_020187.3:c.29C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020187.3(HMCES):​c.29C>T​(p.Pro10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HMCES NM_020187.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

Genes affected

HMCES (HGNC:24446): (5-hydroxymethylcytosine binding, ES cell specific) Enables single-stranded DNA binding activity. Involved in cellular response to DNA damage stimulus and protein-DNA covalent cross-linking. Located in replication fork. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020187.3. 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
	HMCES	NM_020187.3	MANE Select	c.29C>T	p.Pro10Leu	missense	Exon 2 of 7	NP_064572.2	Q96FZ2
	HMCES	NM_001006109.1		c.29C>T	p.Pro10Leu	missense	Exon 2 of 7	NP_001006109.1	Q96FZ2
	HMCES	NM_001370343.1		c.29C>T	p.Pro10Leu	missense	Exon 2 of 7	NP_001357272.1	Q96FZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCES	ENST00000383463.9	TSL:1 MANE Select	c.29C>T	p.Pro10Leu	missense	Exon 2 of 7	ENSP00000372955.3	Q96FZ2
	HMCES	ENST00000389735.7	TSL:1	c.29C>T	p.Pro10Leu	missense	Exon 2 of 7	ENSP00000374385.3	Q96FZ2
	HMCES	ENST00000502878.6	TSL:1	c.29C>T	p.Pro10Leu	missense	Exon 2 of 7	ENSP00000426215.1	Q96FZ2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249820 AF XY: 0.00

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.22
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.049
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		2.4
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.042	D
Polyphen		0.99	D
Vest4		0.28
MutPred		0.57		Gain of glycosylation at T15 (P = 0.0058)
MVP		0.54
MPC		0.22
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.43
gMVP		0.50
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1313109323; hg19: chr3-128998604;