NM_001144933.2:c.45G>T

Variant names:

• chr17-62373824-G-T
• rs6504103
• NM_001144933.2:c.45G>T

Variant summary

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

The NM_001144933.2(EFCAB3):​c.45G>T​(p.Lys15Asn) 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. 13/19 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EFCAB3 NM_001144933.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490
• Publications: 3 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]

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=0.15482906).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144933.2. 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_001144933.2		c.45G>T	p.Lys15Asn	missense	Exon 2 of 12	NP_001138405.1	Q8N7B9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB3	ENST00000450662.7	TSL:5	c.45G>T	p.Lys15Asn	missense	Exon 2 of 12	ENSP00000403932.2	Q8N7B9-2
	EFCAB3	ENST00000636041.1	TSL:5	n.274G>T		non_coding_transcript_exon	Exon 4 of 14

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1359772 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 672296

African (AFR) AF: 0.00 AC: 0 AN: 30332

American (AMR) AF: 0.00 AC: 0 AN: 34388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24750

East Asian (EAS) AF: 0.00 AC: 0 AN: 35250

South Asian (SAS) AF: 0.00 AC: 0 AN: 76910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1046886

Other (OTH) AF: 0.00 AC: 0 AN: 56586

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.96
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.49
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.035
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.14	T
Vest4		0.22
MutPred		0.37		Loss of ubiquitination at K15 (P = 0.0155)
MVP		0.13
MPC		0.36
ClinPred		0.41	T
GERP RS		0.79
gMVP		0.19

Splicing

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

Other links and lift over

dbSNP: rs6504103; hg19: chr17-60451185;