5-172194266-T-C

Variant names:

• chr5-172194266-T-C
• NM_001171183.2:c.94T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001171183.2(EFCAB9):​c.94T>C​(p.Tyr32His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFCAB9 NM_001171183.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29

Genes affected

EFCAB9 (HGNC:34530): (EF-hand calcium binding domain 9) This gene encodes a protein with a C-terminal EF-hand calcium-binding domain similar to that found in penta-EF-hand (PEF) protein family members. The EF-hand is a helix-loop-helix structure with a canonical twelve-residue sequence that coordinates a calcium molecule with pentagonal bipyramidal symmetry. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB9	NM_001171183.2	c.94T>C	p.Tyr32His	missense_variant	Exon 1 of 4	ENST00000398186.5	NP_001164654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB9	ENST00000398186.5	c.94T>C	p.Tyr32His	missense_variant	Exon 1 of 4	3	NM_001171183.2	ENSP00000381247.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.94T>C (p.Y32H) alteration is located in exon 1 (coding exon 1) of the EFCAB9 gene. This alteration results from a T to C substitution at nucleotide position 94, causing the tyrosine (Y) at amino acid position 32 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.036
Eigen_PC	Benign	-0.079
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Vest4		0.43
MutPred		0.73		Loss of stability (P = 0.0585);
MVP		0.048
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.42
gMVP		0.92

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-171621270;