6-31876147-C-A

Variant names:

• chr6-31876147-C-A
• rs2736428
• NM_025257.3:c.90-18G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025257.3(SLC44A4):​c.90-18G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC44A4 NM_025257.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.90-18G>T		intron	N/A	NP_079533.2	A0A140VJH4
	SLC44A4	NM_001178044.2		c.90-18G>T		intron	N/A	NP_001171515.1	Q53GD3-4
	SLC44A4	NM_001178045.2		c.-139-18G>T		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.90-18G>T		intron	N/A	ENSP00000229729.6	Q53GD3-1
	SLC44A4	ENST00000414427.1	TSL:5	c.75-18G>T		intron	N/A	ENSP00000398901.1	H0Y5I3
	SLC44A4	ENST00000882851.1		c.90-18G>T		intron	N/A	ENSP00000552910.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.48
DANN	Benign	0.79
PhyloP100		-2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2736428;

hg19: chr6-31843924;