NM_152512.4:c.1372T>C

Variant names:

• chr22-39744131-A-G
• rs751467701
• NM_152512.4:c.1372T>C

Variant summary

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

The NM_152512.4(ENTHD1):​c.1372T>C​(p.Ser458Pro) 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. 16/22 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: ENTHD1 NM_152512.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.653
• Publications: 0 publications found

Genes affected

ENTHD1 (HGNC:26352): (ENTH domain containing 1) Predicted to enable clathrin binding activity and phospholipid binding activity. Predicted to be involved in endocytosis. Predicted to be part of clathrin vesicle coat. Predicted to be active in endosome and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.049827337).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152512.4. 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
	ENTHD1	NM_152512.4	MANE Select	c.1372T>C	p.Ser458Pro	missense	Exon 7 of 7	NP_689725.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTHD1	ENST00000325157.7	TSL:1 MANE Select	c.1372T>C	p.Ser458Pro	missense	Exon 7 of 7	ENSP00000317431.6	Q8IYW4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251134 AF XY: 0.00000737

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.078
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.0
DANN	Benign	0.85
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.85	L
PhyloP100		0.65
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.015
Sift	Benign	0.37	T
Sift4G	Benign	0.44	T
Polyphen		0.0060	B
Vest4		0.046
MutPred		0.20		Loss of stability (P = 0.0384)
MVP		0.095
MPC		0.086
ClinPred		0.023	T
GERP RS		0.47
Varity_R		0.064
gMVP		0.035
Mutation Taster		=99/1	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: rs751467701; hg19: chr22-40140136;