14-89931629-G-C

Variant names:

• chr14-89931629-G-C
• rs757985158
• NM_145231.4:c.322C>G

Variant summary

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

The NM_145231.4(EFCAB11):​c.322C>G​(p.Arg108Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,682 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. R108H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EFCAB11 NM_145231.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 2 publications found

Genes affected

EFCAB11 (HGNC:20357): (EF-hand calcium binding domain 11) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259053 (HGNC:):

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_145231.4. 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
	EFCAB11	NM_145231.4	MANE Select	c.322C>G	p.Arg108Gly	missense splice_region	Exon 5 of 6	NP_660274.1	Q9BUY7-1
	EFCAB11	NM_001284266.2		c.322C>G	p.Arg108Gly	missense splice_region	Exon 5 of 6	NP_001271195.1	Q9BUY7-5
	EFCAB11	NM_001284269.2		c.250C>G	p.Arg84Gly	missense splice_region	Exon 5 of 6	NP_001271198.1	Q9BUY7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB11	ENST00000316738.12	TSL:2 MANE Select	c.322C>G	p.Arg108Gly	missense splice_region	Exon 5 of 6	ENSP00000326267.7	Q9BUY7-1
	EFCAB11	ENST00000555872.5	TSL:1	c.250C>G	p.Arg84Gly	missense splice_region	Exon 5 of 6	ENSP00000452320.1	Q9BUY7-2
	EFCAB11	ENST00000556005.1	TSL:1	c.250C>G	p.Arg84Gly	missense splice_region	Exon 5 of 6	ENSP00000452143.1	Q9BUY7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250684 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460682 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726684

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.0000224 AC: 1 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111258

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.079	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	0.069	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.9
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.61		Gain of catalytic residue at Y107 (P = 9e-04)
MVP		0.86
MPC		0.37
ClinPred		0.97	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.64
Mutation Taster		=33/67	disease causing

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: rs757985158; hg19: chr14-90397973;