17-29969075-G-T

Variant names:

• chr17-29969075-G-T
• rs764517431
• NM_198529.4:c.475G>T

Variant summary

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

The NM_198529.4(EFCAB5):​c.475G>T​(p.Glu159*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EFCAB5 NM_198529.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.475G>T	p.Glu159*	stop_gained	Exon 4 of 23	NP_940931.3	A4FU69-1
	EFCAB5	NM_001145053.2		c.307G>T	p.Glu103*	stop_gained	Exon 4 of 15	NP_001138525.2	A4FU69-5
	EFCAB5	NR_026738.2		n.638G>T		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.475G>T	p.Glu159*	stop_gained	Exon 4 of 23	ENSP00000378312.3	A4FU69-1
	EFCAB5	ENST00000440741.7	TSL:1	n.475G>T		non_coding_transcript_exon	Exon 4 of 16	ENSP00000393095.2	A4FU69-2
	EFCAB5	ENST00000536908.6	TSL:2	c.307G>T	p.Glu103*	stop_gained	Exon 4 of 15	ENSP00000440619.2	A4FU69-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460234 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726156

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111328

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	35
DANN	Uncertain	1.0
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.92	D
PhyloP100		3.2
Vest4		0.30
GERP RS		3.5
PromoterAI		-0.010	Neutral

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: rs764517431; hg19: chr17-28296093;