1-36322350-G-A

Position:

• chr1-36322350-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_001304762.2(EVA1B):​c.443C>T​(p.Thr148Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000035 in 1,430,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: EVA1B NM_001304762.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.25

Genes affected

EVA1B (HGNC:25558): (eva-1 homolog B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SH3D21 (HGNC:26236): (SH3 domain containing 21) Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVA1B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a modified_residue Phosphothreonine (size 0) in uniprot entity EVA1B_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3814785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVA1B	NM_001304762.2	c.443C>T	p.Thr148Met	missense_variant	3/3	ENST00000490466.2	NP_001291691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVA1B	ENST00000490466.2	c.443C>T	p.Thr148Met	missense_variant	3/3	2	NM_001304762.2	ENSP00000507013.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000350 AC: 5 AN: 1430508 Hom.: 0 Cov.: 36 AF XY: 0.00000141 AC XY: 1 AN XY: 710820

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000362

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.443C>T (p.T148M) alteration is located in exon 3 (coding exon 2) of the EVA1B gene. This alteration results from a C to T substitution at nucleotide position 443, causing the threonine (T) at amino acid position 148 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.14		Loss of glycosylation at T148 (P = 0.0225);
MVP		0.22
MPC		1.2
ClinPred		0.89	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.27
gMVP		0.67

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: rs1646478234; hg19: chr1-36787951;