6-52490267-G-T

Variant names:

• chr6-52490267-G-T
• NM_018100.4:c.1768G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018100.4(EFHC1):​c.1768G>T​(p.Ala590Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EFHC1 NM_018100.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

Genes affected

EFHC1 (HGNC:16406): (EF-hand domain containing 1) This gene encodes an EF-hand-containing calcium binding protein. The encoded protein likely plays a role in calcium homeostasis. Mutations in this gene have been associated with susceptibility to juvenile myoclonic epilepsy and juvenile absence epilepsy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040132046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFHC1	NM_018100.4	c.1768G>T	p.Ala590Ser	missense_variant	Exon 10 of 11	ENST00000371068.11	NP_060570.2
EFHC1	NM_001172420.2	c.1711G>T	p.Ala571Ser	missense_variant	Exon 11 of 12		NP_001165891.1
EFHC1	NR_033327.2	n.3094G>T		non_coding_transcript_exon_variant	Exon 9 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11	c.1768G>T	p.Ala590Ser	missense_variant	Exon 10 of 11	1	NM_018100.4	ENSP00000360107.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461824 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.76
DEOGEN2	Benign	0.061	.;.;T;T;T;T;.;T;.;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.84	T;.;T;T;T;T;T;T;.;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.040	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	.;.;L;.;.;.;.;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.21	.;.;N;.;.;.;.;.;.;N
REVEL	Benign	0.025
Sift	Benign	0.69	.;.;T;.;.;.;.;.;.;T
Sift4G	Benign	0.70	.;.;T;.;.;.;.;.;.;T
Polyphen		0.0070	.;.;B;.;.;.;.;.;.;.
Vest4		0.17, 0.17
MutPred		0.32		.;.;Gain of disorder (P = 0.0274);Gain of disorder (P = 0.0274);Gain of disorder (P = 0.0274);.;Gain of disorder (P = 0.0274);.;.;.;
MVP		0.36
MPC		0.078
ClinPred		0.062	T
GERP RS		2.8
Varity_R		0.058
gMVP		0.060

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: chr6-52355065;