chr17-29969207-G-A

Variant names:

• chr17-29969207-G-A
• NM_198529.4:c.607G>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.607G>A​(p.Asp203Asn) 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. 14/22 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: EFCAB5 NM_198529.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.196
• 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=0.14657003).

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.607G>A	p.Asp203Asn	missense	Exon 4 of 23	NP_940931.3	A4FU69-1
	EFCAB5	NM_001145053.2		c.439G>A	p.Asp147Asn	missense	Exon 4 of 15	NP_001138525.2	A4FU69-5
	EFCAB5	NR_026738.2		n.770G>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.607G>A	p.Asp203Asn	missense	Exon 4 of 23	ENSP00000378312.3	A4FU69-1
	EFCAB5	ENST00000588978.1	TSL:1	c.1G>A	p.Asp1Asn	missense	Exon 1 of 12	ENSP00000465109.1	K7EJC3
	EFCAB5	ENST00000440741.7	TSL:1	n.607G>A		non_coding_transcript_exon	Exon 4 of 16	ENSP00000393095.2	A4FU69-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.20
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.090
Sift	Benign	0.033	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.17
MutPred		0.27		Gain of helix (P = 0.0199)
MVP		0.24
MPC		0.47
ClinPred		0.65	D
GERP RS		4.0
PromoterAI		-0.0056	Neutral
Varity_R		0.063
gMVP		0.076

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: chr17-28296225;