chr17-47347844-G-T

Variant names:

• chr17-47347844-G-T
• rs149684195
• NM_152347.5:c.554G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152347.5(EFCAB13):​c.554G>T​(p.Arg185Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,377,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R185Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: EFCAB13 NM_152347.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.557
• Publications: 0 publications found

Genes affected

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.554G>T	p.Arg185Leu	missense	Exon 9 of 25	NP_689560.3
	EFCAB13	NM_001426585.1		c.554G>T	p.Arg185Leu	missense	Exon 8 of 23	NP_001413514.1
	EFCAB13	NM_001426587.1		c.554G>T	p.Arg185Leu	missense	Exon 9 of 23	NP_001413516.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB13	ENST00000331493.7	TSL:1 MANE Select	c.554G>T	p.Arg185Leu	missense	Exon 9 of 25	ENSP00000332111.2	Q8IY85-1
	EFCAB13	ENST00000517484.5	TSL:2	c.517+2746G>T		intron	N/A	ENSP00000430048.1	Q8IY85-2
	EFCAB13	ENST00000517310.5	TSL:2	c.73+2746G>T		intron	N/A	ENSP00000466136.1	K7ELL9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1377690 Hom.: 0 Cov.: 30 AF XY: 0.00000295 AC XY: 2 AN XY: 676892

African (AFR) AF: 0.00 AC: 0 AN: 32280

American (AMR) AF: 0.00 AC: 0 AN: 41366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24476

East Asian (EAS) AF: 0.00 AC: 0 AN: 38204

South Asian (SAS) AF: 0.0000142 AC: 1 AN: 70240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5490

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1058248

Other (OTH) AF: 0.0000177 AC: 1 AN: 56444

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.56
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.32
MutPred		0.44		Gain of helix (P = 0.0117)
MVP		0.17
MPC		0.64
ClinPred		0.68	D
GERP RS		-0.025
Varity_R		0.18
gMVP		0.21
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.62		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.62		Position offset: -36

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs149684195; hg19: chr17-45425210; COSMIC: COSV104644447; COSMIC: COSV104644447;