chr17-47341974-G-T

Variant names:

• chr17-47341974-G-T
• rs754146644
• NM_152347.5:c.245G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152347.5(EFCAB13):​c.245G>T​(p.Gly82Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,445,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: EFCAB13 NM_152347.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.330

Genes affected

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

ENSG00000259753 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038889408).
• BP6: Variant 17-47341974-G-T is Benign according to our data. Variant chr17-47341974-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3506848.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB13	NM_152347.5	c.245G>T	p.Gly82Val	missense_variant	Exon 6 of 25	ENST00000331493.7	NP_689560.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB13	ENST00000331493.7	c.245G>T	p.Gly82Val	missense_variant	Exon 6 of 25	1	NM_152347.5	ENSP00000332111.2
ENSG00000259753	ENST00000560629.1	n.*234G>T		non_coding_transcript_exon_variant	Exon 17 of 18	2		ENSP00000456711.2
ENSG00000259753	ENST00000560629.1	n.*234G>T		3_prime_UTR_variant	Exon 17 of 18	2		ENSP00000456711.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000210 AC: 5 AN: 237582 Hom.: 0 AF XY: 0.0000155 AC XY: 2 AN XY: 128646

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000964

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000484 AC: 7 AN: 1445398 Hom.: 0 Cov.: 28 AF XY: 0.00000278 AC XY: 2 AN XY: 718562

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000713

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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.: 32

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 28, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.1
DANN	Benign	0.24
DEOGEN2	Benign	0.0039	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.46	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.088
Sift	Benign	0.28	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0010	B;.
Vest4		0.15
MutPred		0.25		Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);
MVP		0.014
MPC		0.18
ClinPred		0.029	T
GERP RS		0.30
Varity_R		0.063
gMVP		0.022

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: rs754146644; hg19: chr17-45419340;