chr6-31864579-C-CAAAA

Variant names:

• chr6-31864579-C-CAAAA
• rs5875335
• NM_025257.3:c.2011+69_2011+72dupTTTT

Variant summary

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

The NM_025257.3(SLC44A4):​c.2011+69_2011+72dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• 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 0 ACMG points.

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+69_2011+72dupTTTT		intron	N/A	NP_079533.2	A0A140VJH4
	SLC44A4	NM_001178044.2		c.1885+69_1885+72dupTTTT		intron	N/A	NP_001171515.1	Q53GD3-4
	SLC44A4	NM_001178045.2		c.1783+69_1783+72dupTTTT		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+69_2011+72dupTTTT		intron	N/A	ENSP00000229729.6	Q53GD3-1
	SLC44A4	ENST00000882851.1		c.2011+69_2011+72dupTTTT		intron	N/A	ENSP00000552910.1
	SLC44A4	ENST00000882853.1		c.2011+69_2011+72dupTTTT		intron	N/A	ENSP00000552912.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 129538 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000133 AC: 15 AN: 1130220 Hom.: 0 Cov.: 0 AF XY: 0.0000175 AC XY: 10 AN XY: 572880

⚠️ 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: 25432

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: 0.0000401 AC: 3 AN: 74798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46862

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

European-Non Finnish (NFE) AF: 0.0000108 AC: 9 AN: 833190

Other (OTH) AF: 0.0000614 AC: 3 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 129538 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 62292

African (AFR) AF: 0.00 AC: 0 AN: 36706

American (AMR) AF: 0.00 AC: 0 AN: 12848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3070

East Asian (EAS) AF: 0.00 AC: 0 AN: 4510

South Asian (SAS) AF: 0.00 AC: 0 AN: 4142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58496

Other (OTH) AF: 0.00 AC: 0 AN: 1738

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;