17-47342006-G-T

Variant names:

• chr17-47342006-G-T
• rs777824600
• NM_152347.5:c.277G>T

Variant summary

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

The NM_152347.5(EFCAB13):​c.277G>T​(p.Val93Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,443,556 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V93I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: EFCAB13 NM_152347.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352
• Publications: 0 publications found

Genes affected

EFCAB13 (HGNC:26864): (EF-hand calcium binding domain 13)

ENSG00000259753 (HGNC:):

EFCAB13-DT (HGNC:55338): (EFCAB13 divergent transcript)

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=0.095122844).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152347.5. 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
	EFCAB13	NM_152347.5	MANE Select	c.277G>T	p.Val93Leu	missense	Exon 6 of 25	NP_689560.3
	EFCAB13	NM_001426585.1		c.277G>T	p.Val93Leu	missense	Exon 5 of 23	NP_001413514.1
	EFCAB13	NM_001426586.1		c.277G>T	p.Val93Leu	missense	Exon 6 of 23	NP_001413515.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB13	ENST00000331493.7	TSL:1 MANE Select	c.277G>T	p.Val93Leu	missense	Exon 6 of 25	ENSP00000332111.2	Q8IY85-1
	ENSG00000259753	ENST00000560629.1	TSL:2	n.*266G>T		non_coding_transcript_exon	Exon 17 of 18	ENSP00000456711.2	H3BM21
	ENSG00000259753	ENST00000560629.1	TSL:2	n.*266G>T		3_prime_UTR	Exon 17 of 18	ENSP00000456711.2	H3BM21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000419 AC: 1 AN: 238492 AF XY: 0.00000775

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000906

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1443556 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 718050

African (AFR) AF: 0.00 AC: 0 AN: 32402

American (AMR) AF: 0.00 AC: 0 AN: 41676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25862

East Asian (EAS) AF: 0.00 AC: 0 AN: 39234

South Asian (SAS) AF: 0.00 AC: 0 AN: 82338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00000363 AC: 4 AN: 1103284

Other (OTH) AF: 0.00 AC: 0 AN: 59738

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000193 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	13
DANN	Benign	0.52
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.35
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.046	D
Polyphen		0.36	B
Vest4		0.18
MutPred		0.25		Loss of sheet (P = 0.0181)
MVP		0.072
MPC		0.14
ClinPred		0.083	T
GERP RS		0.65
Varity_R		0.14
gMVP		0.014

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs777824600; hg19: chr17-45419372;