6-31864579-CAAAAAAAA-CAAAAA

Variant names:

• chr6-31864579-CAAA-C
• rs5875335
• NM_025257.3:c.2011+70_2011+72delTTT

Variant summary

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

The NM_025257.3(SLC44A4):​c.2011+70_2011+72delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000323 in 1,128,312 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.00032 (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+70_2011+72delTTT		intron	N/A	NP_079533.2	A0A140VJH4
	SLC44A4	NM_001178044.2		c.1885+70_1885+72delTTT		intron	N/A	NP_001171515.1	Q53GD3-4
	SLC44A4	NM_001178045.2		c.1783+70_1783+72delTTT		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+70_2011+72delTTT		intron	N/A	ENSP00000229729.6	Q53GD3-1
	SLC44A4	ENST00000882851.1		c.2011+70_2011+72delTTT		intron	N/A	ENSP00000552910.1
	SLC44A4	ENST00000882853.1		c.2011+70_2011+72delTTT		intron	N/A	ENSP00000552912.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 129526 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: 0.000323 AC: 364 AN: 1128312 Hom.: 0 AF XY: 0.000292 AC XY: 167 AN XY: 571882

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

African (AFR) AF: 0.000315 AC: 8 AN: 25416

American (AMR) AF: 0.000301 AC: 11 AN: 36530

Ashkenazi Jewish (ASJ) AF: 0.000221 AC: 5 AN: 22660

East Asian (EAS) AF: 0.0000532 AC: 2 AN: 37572

South Asian (SAS) AF: 0.0000937 AC: 7 AN: 74692

European-Finnish (FIN) AF: 0.0000641 AC: 3 AN: 46776

Middle Eastern (MID) AF: 0.000236 AC: 1 AN: 4244

European-Non Finnish (NFE) AF: 0.000380 AC: 316 AN: 831694

Other (OTH) AF: 0.000226 AC: 11 AN: 48728

⚠️ 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: 129526 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 62286

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: 7044

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58490

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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs5875335; hg19: chr6-31832356;