17-29968848-C-G

Position:

• chr17-29968848-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000394835.8(EFCAB5):​c.248C>G​(p.Thr83Ser) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFCAB5 ENST00000394835.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.32

Genes affected

EFCAB5 (HGNC:24801): (EF-hand calcium binding domain 5) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07605255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB5	NM_198529.4	c.248C>G	p.Thr83Ser	missense_variant	4/23	ENST00000394835.8	NP_940931.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB5	ENST00000394835.8	c.248C>G	p.Thr83Ser	missense_variant	4/23	1	NM_198529.4	ENSP00000378312	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Dec 21, 2022

The c.248C>G (p.T83S) alteration is located in exon 4 (coding exon 4) of the EFCAB5 gene. This alteration results from a C to G substitution at nucleotide position 248, causing the threonine (T) at amino acid position 83 to be replaced by a serine (S). 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	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.091
DANN	Benign	0.61
DEOGEN2	Benign	0.00077	.;.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.48	T;T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.076	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	.;.;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.6	N;N;N;.
REVEL	Benign	0.071
Sift	Benign	0.063	T;D;D;.
Sift4G	Benign	0.74	T;T;T;.
Polyphen		0.0070	.;.;B;.
Vest4		0.096, 0.059
MutPred		0.085		.;.;Gain of phosphorylation at T83 (P = 0.0679);.;
MVP		0.13
MPC		0.12
ClinPred		0.093	T
GERP RS		-5.2
Varity_R		0.030
gMVP		0.014

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-28295866;