17-47341974-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152347.5(EFCAB13):​c.245G>A​(p.Gly82Glu) 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. 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. G82V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFCAB13 NM_152347.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05015418).

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.245G>A	p.Gly82Glu	missense	Exon 6 of 25	NP_689560.3
	EFCAB13	NM_001426585.1		c.245G>A	p.Gly82Glu	missense	Exon 5 of 23	NP_001413514.1
	EFCAB13	NM_001426586.1		c.245G>A	p.Gly82Glu	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.245G>A	p.Gly82Glu	missense	Exon 6 of 25	ENSP00000332111.2	Q8IY85-1
	ENSG00000259753	ENST00000560629.1	TSL:2	n.*234G>A		non_coding_transcript_exon	Exon 17 of 18	ENSP00000456711.2	H3BM21
	ENSG00000259753	ENST00000560629.1	TSL:2	n.*234G>A		3_prime_UTR	Exon 17 of 18	ENSP00000456711.2	H3BM21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.1
DANN	Benign	0.29
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.33
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Benign	0.078	T
Sift4G	Benign	0.52	T
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.25		Gain of helix (P = 0.0078)
MVP		0.014
MPC		0.19
ClinPred		0.025	T
GERP RS		0.30
Varity_R		0.061
gMVP		0.011

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: rs754146644; hg19: chr17-45419340;