NM_198529.4:c.83C>T

Variant names:

• chr17-29942280-C-T
• rs1377182586
• NM_198529.4:c.83C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198529.4(EFCAB5):​c.83C>T​(p.Thr28Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: EFCAB5 NM_198529.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

Genes affected

EFCAB5 (HGNC:24801): (EF-hand calcium binding domain 5) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058766544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB5	NM_198529.4	c.83C>T	p.Thr28Ile	missense_variant	Exon 2 of 23	ENST00000394835.8	NP_940931.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB5	ENST00000394835.8	c.83C>T	p.Thr28Ile	missense_variant	Exon 2 of 23	1	NM_198529.4	ENSP00000378312.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.0090
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.017	B
Vest4		0.071
MutPred		0.18		Gain of helix (P = 0.0425);
MVP		0.072
MPC		0.099
ClinPred		0.063	T
GERP RS		-1.5
Varity_R		0.051
gMVP		0.069

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

Publications

LitVar

Other links and lift over

dbSNP: rs1377182586; hg19: chr17-28269298;