chr22-39887423-A-G

Variant names:

• chr22-39887423-A-G
• rs17319801
• NM_152512.4:c.326T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152512.4(ENTHD1):​c.326T>C​(p.Ile109Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0471 in 1,610,882 control chromosomes in the GnomAD database, including 2,053 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.037 (144 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1909 hom.)
• Consequence: ENTHD1 NM_152512.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025298893).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0742 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTHD1	NM_152512.4	MANE Select	c.326T>C	p.Ile109Thr	missense	Exon 2 of 7	NP_689725.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTHD1	ENST00000325157.7	TSL:1 MANE Select	c.326T>C	p.Ile109Thr	missense	Exon 2 of 7	ENSP00000317431.6

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5693 AN: 152092 Hom.: 144 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0738

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.0455

GnomAD2 exomes AF: 0.0471 AC: 11699 AN: 248612 AF XY: 0.0484

Gnomad AFR exome AF: 0.00851

Gnomad AMR exome AF: 0.0756

Gnomad ASJ exome AF: 0.0330

Gnomad EAS exome AF: 0.000709

Gnomad FIN exome AF: 0.0284

Gnomad NFE exome AF: 0.0488

Gnomad OTH exome AF: 0.0508

GnomAD4 exome AF: 0.0481 AC: 70104 AN: 1458672 Hom.: 1909 Cov.: 31 AF XY: 0.0487 AC XY: 35337 AN XY: 725626

African (AFR) AF: 0.00857 AC: 285 AN: 33264

American (AMR) AF: 0.0808 AC: 3573 AN: 44222

Ashkenazi Jewish (ASJ) AF: 0.0342 AC: 888 AN: 25938

East Asian (EAS) AF: 0.000529 AC: 21 AN: 39678

South Asian (SAS) AF: 0.0767 AC: 6576 AN: 85752

European-Finnish (FIN) AF: 0.0286 AC: 1522 AN: 53242

Middle Eastern (MID) AF: 0.0308 AC: 177 AN: 5754

European-Non Finnish (NFE) AF: 0.0489 AC: 54259 AN: 1110590

Other (OTH) AF: 0.0465 AC: 2803 AN: 60232

GnomAD4 genome AF: 0.0374 AC: 5699 AN: 152210 Hom.: 144 Cov.: 32 AF XY: 0.0377 AC XY: 2803 AN XY: 74428

African (AFR) AF: 0.0110 AC: 457 AN: 41534

American (AMR) AF: 0.0740 AC: 1131 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.0808 AC: 389 AN: 4816

European-Finnish (FIN) AF: 0.0277 AC: 293 AN: 10596

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0461 AC: 3137 AN: 68010

Other (OTH) AF: 0.0451 AC: 95 AN: 2108

Alfa AF: 0.0448 Hom.: 482

Bravo AF: 0.0391

TwinsUK AF: 0.0502 AC: 186

ALSPAC AF: 0.0457 AC: 176

ESP6500AA AF: 0.0136 AC: 60

ESP6500EA AF: 0.0484 AC: 416

ExAC AF: 0.0462 AC: 5614

Asia WGS AF: 0.0470 AC: 165 AN: 3478

EpiCase AF: 0.0506

EpiControl AF: 0.0502

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.2
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.11
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.53	P
Vest4		0.037
MPC		0.40
ClinPred		0.040	T
GERP RS		5.4
Varity_R		0.42
gMVP		0.16
Mutation Taster		=95/5	polymorphism (auto)

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: rs17319801; hg19: chr22-40283427; COSMIC: COSV57320698;