17-29969062-T-A

Variant names:

• chr17-29969062-T-A
• rs2085756479
• NM_198529.4:c.462T>A

Variant summary

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

The NM_198529.4(EFCAB5):​c.462T>A​(p.Asp154Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D154Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFCAB5 NM_198529.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55
• 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: 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=0.15047869).

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.462T>A	p.Asp154Glu	missense	Exon 4 of 23	NP_940931.3	A4FU69-1
	EFCAB5	NM_001145053.2		c.294T>A	p.Asp98Glu	missense	Exon 4 of 15	NP_001138525.2	A4FU69-5
	EFCAB5	NR_026738.2		n.625T>A		non_coding_transcript_exon	Exon 4 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB5	ENST00000394835.8	TSL:1 MANE Select	c.462T>A	p.Asp154Glu	missense	Exon 4 of 23	ENSP00000378312.3	A4FU69-1
	EFCAB5	ENST00000440741.7	TSL:1	n.462T>A		non_coding_transcript_exon	Exon 4 of 16	ENSP00000393095.2	A4FU69-2
	EFCAB5	ENST00000536908.6	TSL:2	c.294T>A	p.Asp98Glu	missense	Exon 4 of 15	ENSP00000440619.2	A4FU69-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	Uncertain	0.53
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.6
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.93	P
Vest4		0.43
MutPred		0.28		Gain of helix (P = 0.0117)
MVP		0.36
MPC		0.23
ClinPred		0.80	D
GERP RS		4.5
PromoterAI		0.0016	Neutral
Varity_R		0.27
gMVP		0.068

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

dbSNP: rs2085756479; hg19: chr17-28296080;