chr15-34230149-TA-T

Variant names:

• chr15-34230149-TA-T
• NM_016454.4:c.*368delA

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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]

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
EMC4	NM_016454.4	c.*368delA		splice_region_variant	Exon 5 of 5	ENST00000267750.9	NP_057538.1
SLC12A6	NM_001365088.1	c.*3731delT		3_prime_UTR_variant	Exon 26 of 26	ENST00000354181.8	NP_001352017.1
EMC4	NM_016454.4	c.*368delA		3_prime_UTR_variant	Exon 5 of 5	ENST00000267750.9	NP_057538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMC4	ENST00000267750.9	c.*368delA		splice_region_variant	Exon 5 of 5	1	NM_016454.4	ENSP00000267750.4
SLC12A6	ENST00000354181	c.*3731delT		3_prime_UTR_variant	Exon 26 of 26	1	NM_001365088.1	ENSP00000346112.3
EMC4	ENST00000267750.9	c.*368delA		3_prime_UTR_variant	Exon 5 of 5	1	NM_016454.4	ENSP00000267750.4

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

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

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;