chr17-29943637-A-G

Variant names:

• chr17-29943637-A-G
• NM_198529.4:c.178A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198529.4(EFCAB5):​c.178A>G​(p.Ile60Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,122 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: EFCAB5 NM_198529.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00100
• Publications: 0 publications found

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

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=0.041912347).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198529.4. 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
	EFCAB5	NM_198529.4	MANE Select	c.178A>G	p.Ile60Val	missense	Exon 3 of 23	NP_940931.3	A4FU69-1
	EFCAB5	NM_001145053.2		c.10A>G	p.Ile4Val	missense	Exon 3 of 15	NP_001138525.2	A4FU69-5
	EFCAB5	NR_026738.2		n.341A>G		non_coding_transcript_exon	Exon 3 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB5	ENST00000394835.8	TSL:1 MANE Select	c.178A>G	p.Ile60Val	missense	Exon 3 of 23	ENSP00000378312.3	A4FU69-1
	EFCAB5	ENST00000440741.7	TSL:1	n.178A>G		non_coding_transcript_exon	Exon 3 of 16	ENSP00000393095.2	A4FU69-2
	EFCAB5	ENST00000536908.6	TSL:2	c.10A>G	p.Ile4Val	missense	Exon 3 of 15	ENSP00000440619.2	A4FU69-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424122 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 704692

African (AFR) AF: 0.00 AC: 0 AN: 32632

American (AMR) AF: 0.00 AC: 0 AN: 39102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25448

East Asian (EAS) AF: 0.00 AC: 0 AN: 37986

South Asian (SAS) AF: 0.00 AC: 0 AN: 80764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092306

Other (OTH) AF: 0.00 AC: 0 AN: 59044

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	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.1
DANN	Benign	0.78
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.0010
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.014
Sift	Benign	0.22	T
Sift4G	Benign	1.0	T
Polyphen		0.0070	B
Vest4		0.046
MutPred		0.14		Loss of catalytic residue at L65 (P = 0.0306)
MVP		0.092
MPC		0.083
ClinPred		0.022	T
GERP RS		-0.57
PromoterAI		0.035	Neutral
Varity_R		0.033
gMVP		0.012

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: chr17-28270655;