rs566558212

Variant summary

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

The NM_016454.4(EMC4):​c.*368delA variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000048 in 83,386 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.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

EMC4
NM_016454.4 splice_region

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12
Variant links:
Genes affected
EMC4 (HGNC:28032): (ER membrane protein complex subunit 4) Contributes to membrane insertase activity. Involved in protein insertion into ER membrane by stop-transfer membrane-anchor sequence and tail-anchored membrane protein insertion into ER membrane. Is integral component of endoplasmic reticulum membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]
SLC12A6 (HGNC:10914): (solute carrier family 12 member 6) This gene is a member of the K-Cl cotransporter (KCC) family. K-Cl cotransporters are integral membrane proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The proteins encoded by this gene are activated by cell swelling induced by hypotonic conditions. Alternate splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are associated with agenesis of the corpus callosum with peripheral neuropathy. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

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
EMC4NM_016454.4 linkc.*368delA splice_region_variant Exon 5 of 5 ENST00000267750.9 NP_057538.1 Q5J8M3-1A0A024R9N3
SLC12A6NM_001365088.1 linkc.*3731delT 3_prime_UTR_variant Exon 26 of 26 ENST00000354181.8 NP_001352017.1
EMC4NM_016454.4 linkc.*368delA 3_prime_UTR_variant Exon 5 of 5 ENST00000267750.9 NP_057538.1 Q5J8M3-1A0A024R9N3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EMC4ENST00000267750.9 linkc.*368delA splice_region_variant Exon 5 of 5 1 NM_016454.4 ENSP00000267750.4 Q5J8M3-1
SLC12A6ENST00000354181 linkc.*3731delT 3_prime_UTR_variant Exon 26 of 26 1 NM_001365088.1 ENSP00000346112.3 Q9UHW9-1
EMC4ENST00000267750.9 linkc.*368delA 3_prime_UTR_variant Exon 5 of 5 1 NM_016454.4 ENSP00000267750.4 Q5J8M3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000480
AC:
4
AN:
83386
Hom.:
0
Cov.:
0
AF XY:
0.0000469
AC XY:
2
AN XY:
42648
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000277
Gnomad4 EAS exome
AF:
0.000156
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000361
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

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: chr15-34522350; API