17-62383017-A-C

Variant names:

• chr17-62383017-A-C
• NM_173503.4:c.38A>C

Variant summary

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

The NM_173503.4(EFCAB3):​c.38A>C​(p.Asn13Thr) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFCAB3 NM_173503.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52
• Publications: 0 publications found

Genes affected

EFCAB3 (HGNC:26379): (EF-hand calcium binding domain 3) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

RNU7-52P (HGNC:34148): (RNA, U7 small nuclear 52 pseudogene)

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=0.15431783).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173503.4. 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
	EFCAB3	NM_173503.4	MANE Select	c.38A>C	p.Asn13Thr	missense	Exon 2 of 10	NP_775774.1	Q8N7B9-1
	EFCAB3	NM_001144933.2		c.194A>C	p.Asn65Thr	missense	Exon 4 of 12	NP_001138405.1	Q8N7B9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB3	ENST00000305286.8	TSL:1 MANE Select	c.38A>C	p.Asn13Thr	missense	Exon 2 of 10	ENSP00000302649.3	Q8N7B9-1
	EFCAB3	ENST00000450662.7	TSL:5	c.194A>C	p.Asn65Thr	missense	Exon 4 of 12	ENSP00000403932.2	Q8N7B9-2
	EFCAB3	ENST00000520404.5	TSL:5	c.38A>C	p.Asn13Thr	missense	Exon 2 of 7	ENSP00000429124.1	E5RJB7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.068
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.5
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.050
Sift	Benign	0.065	T
Sift4G	Benign	0.076	T
Polyphen		0.27	B
Vest4		0.24
MutPred		0.24		Gain of loop (P = 0.0097)
MVP		0.77
MPC		0.27
ClinPred		0.69	D
GERP RS		4.4
Varity_R		0.098
gMVP		0.13

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

hg19: chr17-60460378;