chr22-39765534-A-G

Position:

• chr22-39765534-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152512.4(ENTHD1):​c.908T>C​(p.Ile303Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ENTHD1 NM_152512.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03686413).
• BP6: Variant 22-39765534-A-G is Benign according to our data. Variant chr22-39765534-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3275522.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENTHD1	NM_152512.4	c.908T>C	p.Ile303Thr	missense_variant	6/7	ENST00000325157.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENTHD1	ENST00000325157.7	c.908T>C	p.Ile303Thr	missense_variant	6/7	1	NM_152512.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250352 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135512

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.19
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.6	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.050
Sift	Benign	1.0	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.34		Loss of helix (P = 0.0017);
MVP		0.040
MPC		0.082
ClinPred		0.044	T
GERP RS		1.2
Varity_R		0.021
gMVP		0.054

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: rs757998756; hg19: chr22-40161539;