17-47335311-A-C

Variant names:

• chr17-47335311-A-C
• rs770550643
• NM_152347.5:c.146A>C

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.146A>C​(p.Glu49Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. E49V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EFCAB13 NM_152347.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• 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: 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=0.038558334).

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.146A>C	p.Glu49Ala	missense	Exon 5 of 25	NP_689560.3
	EFCAB13	NM_001426585.1		c.146A>C	p.Glu49Ala	missense	Exon 4 of 23	NP_001413514.1
	EFCAB13	NM_001426586.1		c.146A>C	p.Glu49Ala	missense	Exon 5 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.146A>C	p.Glu49Ala	missense	Exon 5 of 25	ENSP00000332111.2	Q8IY85-1
	ENSG00000259753	ENST00000560629.1	TSL:2	n.*135A>C		non_coding_transcript_exon	Exon 16 of 18	ENSP00000456711.2	H3BM21
	ENSG00000259753	ENST00000560629.1	TSL:2	n.*135A>C		3_prime_UTR	Exon 16 of 18	ENSP00000456711.2	H3BM21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000413 AC: 1 AN: 242056 AF XY: 0.00000765

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: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454400 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723054

African (AFR) AF: 0.00 AC: 0 AN: 33112

American (AMR) AF: 0.00 AC: 0 AN: 43186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25946

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.00 AC: 0 AN: 83774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109928

Other (OTH) AF: 0.00 AC: 0 AN: 60164

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.59
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.091
Sift	Benign	0.041	D
Sift4G	Uncertain	0.031	D
Polyphen		0.0	B
Vest4		0.049
MutPred		0.21		Gain of helix (P = 0.0199)
MVP		0.014
MPC		0.15
ClinPred		0.054	T
GERP RS		-2.4
Varity_R		0.043
gMVP		0.020

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs770550643; hg19: chr17-45412677;