17-29969150-C-T

Variant names:

• chr17-29969150-C-T
• rs143150190
• NM_198529.4:c.550C>T

Variant summary

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

The NM_198529.4(EFCAB5):​c.550C>T​(p.Pro184Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,578 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P184H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EFCAB5 NM_198529.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81
• 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.550C>T	p.Pro184Ser	missense	Exon 4 of 23	NP_940931.3	A4FU69-1
	EFCAB5	NM_001145053.2		c.382C>T	p.Pro128Ser	missense	Exon 4 of 15	NP_001138525.2	A4FU69-5
	EFCAB5	NR_026738.2		n.713C>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.550C>T	p.Pro184Ser	missense	Exon 4 of 23	ENSP00000378312.3	A4FU69-1
	EFCAB5	ENST00000440741.7	TSL:1	n.550C>T		non_coding_transcript_exon	Exon 4 of 16	ENSP00000393095.2	A4FU69-2
	EFCAB5	ENST00000536908.6	TSL:2	c.382C>T	p.Pro128Ser	missense	Exon 4 of 15	ENSP00000440619.2	A4FU69-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461578 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727062

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111814

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.8
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.15
Sift	Uncertain	0.020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.45		Loss of loop (P = 0.0073)
MVP		0.54
MPC		0.47
ClinPred		0.88	D
GERP RS		4.6
PromoterAI		-0.019	Neutral
Varity_R		0.18
gMVP		0.29
Mutation Taster		=94/6	polymorphism

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: rs143150190; hg19: chr17-28296168;