17-62406536-C-T

Variant names:

• chr17-62406536-C-T
• rs776589359
• NM_173503.4:c.545C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173503.4(EFCAB3):​c.545C>T​(p.Thr182Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: EFCAB3 NM_173503.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0650
• Publications: 0 publications found

Genes affected

EFCAB3 (HGNC:26379): (EF-hand calcium binding domain 3) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13387728).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173503.4. 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
	EFCAB3	NM_173503.4	MANE Select	c.545C>T	p.Thr182Ile	missense	Exon 7 of 10	NP_775774.1	Q8N7B9-1
	EFCAB3	NM_001144933.2		c.701C>T	p.Thr234Ile	missense	Exon 9 of 12	NP_001138405.1	Q8N7B9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB3	ENST00000305286.8	TSL:1 MANE Select	c.545C>T	p.Thr182Ile	missense	Exon 7 of 10	ENSP00000302649.3	Q8N7B9-1
	EFCAB3	ENST00000450662.7	TSL:5	c.701C>T	p.Thr234Ile	missense	Exon 9 of 12	ENSP00000403932.2	Q8N7B9-2
	EFCAB3	ENST00000636041.1	TSL:5	n.930C>T		non_coding_transcript_exon	Exon 11 of 14

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461804 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111958

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.8
DANN	Benign	0.93
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.065
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.040
Sift	Benign	0.14	T
Sift4G	Uncertain	0.038	D
Polyphen		0.089	B
Vest4		0.34
MutPred		0.44		Gain of helix (P = 0.0164)
MVP		0.69
MPC		0.18
ClinPred		0.051	T
GERP RS		1.5
Varity_R		0.032
gMVP		0.23
Mutation Taster		=85/15	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: rs776589359; hg19: chr17-60483897; COSMIC: COSV59505285; COSMIC: COSV59505285;