NM_025257.3:c.2011+68_2011+72delTTTTT

Variant names:

• chr6-31864579-CAAAAA-C
• rs5875335
• NM_025257.3:c.2011+68_2011+72delTTTTT

Variant summary

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

The NM_025257.3(SLC44A4):​c.2011+68_2011+72delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000885 in 1,130,272 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: SLC44A4 NM_025257.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323
• Publications: 0 publications found

Genes affected

SLC44A4 (HGNC:13941): (solute carrier family 44 member 4) The protein encoded by this gene may be a sodium-dependent transmembrane transport protein involved in the uptake of choline by cholinergic neurons. Defects in this gene can cause sialidosis, a lysosomal storage disease. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SLC44A4 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal dominant 72

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

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_025257.3. 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
	SLC44A4	NM_025257.3	MANE Select	c.2011+68_2011+72delTTTTT		intron	N/A	NP_079533.2	A0A140VJH4
	SLC44A4	NM_001178044.2		c.1885+68_1885+72delTTTTT		intron	N/A	NP_001171515.1	Q53GD3-4
	SLC44A4	NM_001178045.2		c.1783+68_1783+72delTTTTT		intron	N/A	NP_001171516.1	A0A1U9X8K7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A4	ENST00000229729.11	TSL:1 MANE Select	c.2011+68_2011+72delTTTTT		intron	N/A	ENSP00000229729.6	Q53GD3-1
	SLC44A4	ENST00000882851.1		c.2011+68_2011+72delTTTTT		intron	N/A	ENSP00000552910.1
	SLC44A4	ENST00000882853.1		c.2011+68_2011+72delTTTTT		intron	N/A	ENSP00000552912.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 8.85e-7 AC: 1 AN: 1130272 Hom.: 0 AF XY: 0.00000175 AC XY: 1 AN XY: 572908

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25434

American (AMR) AF: 0.00 AC: 0 AN: 36562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22694

East Asian (EAS) AF: 0.00 AC: 0 AN: 37590

South Asian (SAS) AF: 0.00 AC: 0 AN: 74806

European-Finnish (FIN) AF: 0.0000213 AC: 1 AN: 46860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 833234

Other (OTH) AF: 0.00 AC: 0 AN: 48844

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5875335; hg19: chr6-31832356;