rs779979711

Variant names:

• chr3-129288972-C-A
• rs779979711
• NM_020187.3:c.302C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-129288972-C-A
• chr3-129288972-C-T

Variant summary

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

The NM_020187.3(HMCES):​c.302C>A​(p.Thr101Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000215 in 1,580,082 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T101I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: HMCES NM_020187.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.96
• 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.302C>A	p.Thr101Asn	missense	Exon 3 of 7	NP_064572.2	Q96FZ2
	HMCES	NM_001006109.1		c.302C>A	p.Thr101Asn	missense	Exon 3 of 7	NP_001006109.1	Q96FZ2
	HMCES	NM_001370343.1		c.302C>A	p.Thr101Asn	missense	Exon 3 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.302C>A	p.Thr101Asn	missense	Exon 3 of 7	ENSP00000372955.3	Q96FZ2
	HMCES	ENST00000389735.7	TSL:1	c.302C>A	p.Thr101Asn	missense	Exon 3 of 7	ENSP00000374385.3	Q96FZ2
	HMCES	ENST00000502878.6	TSL:1	c.302C>A	p.Thr101Asn	missense	Exon 3 of 7	ENSP00000426215.1	Q96FZ2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152046 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250636 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000217 AC: 31 AN: 1428036 Hom.: 0 Cov.: 30 AF XY: 0.0000255 AC XY: 18 AN XY: 706880

African (AFR) AF: 0.00 AC: 0 AN: 33128

American (AMR) AF: 0.00 AC: 0 AN: 44326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25456

East Asian (EAS) AF: 0.00 AC: 0 AN: 39108

South Asian (SAS) AF: 0.00 AC: 0 AN: 83294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.0000267 AC: 29 AN: 1086090

Other (OTH) AF: 0.0000341 AC: 2 AN: 58578

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152046 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74258

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

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	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Benign	0.66
DEOGEN2	Benign	0.040	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0062	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.0
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.17
Sift	Benign	0.41	T
Sift4G	Benign	1.0	T
Polyphen		1.0	D
Vest4		0.27
MutPred		0.78		Gain of glycosylation at T101 (P = 0.0421)
MVP		0.72
MPC		0.33
ClinPred		0.30	T
GERP RS		5.1
Varity_R		0.54
gMVP		0.67
Mutation Taster		=40/60	disease causing

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: rs779979711; hg19: chr3-129007815;