rs73402188

Variant names:

• chr6-31864537-G-A
• rs73402188
• NM_025257.3:c.2011+115C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31864537-G-A
• chr6-31864537-G-C
• chr6-31864537-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_025257.3(SLC44A4):​c.2011+115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 989,516 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (67 hom., cov: 31)
  • Exomes 𝑓: 0.0020 (40 hom.)
• Consequence: SLC44A4 NM_025257.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.13
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-31864537-G-A is Benign according to our data. Variant chr6-31864537-G-A is described in ClinVar as Benign. ClinVar VariationId is 1226387.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.

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+115C>T		intron	N/A	NP_079533.2	A0A140VJH4
	SLC44A4	NM_001178044.2		c.1885+115C>T		intron	N/A	NP_001171515.1	Q53GD3-4
	SLC44A4	NM_001178045.2		c.1783+115C>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.2011+115C>T		intron	N/A	ENSP00000229729.6	Q53GD3-1
	SLC44A4	ENST00000882851.1		c.2011+115C>T		intron	N/A	ENSP00000552910.1
	SLC44A4	ENST00000882853.1		c.2011+115C>T		intron	N/A	ENSP00000552912.1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2705 AN: 149874 Hom.: 68 Cov.: 31

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00744

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000839

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000310

Gnomad OTH AF: 0.0175

GnomAD4 exome AF: 0.00201 AC: 1687 AN: 839542 Hom.: 40 Cov.: 11 AF XY: 0.00172 AC XY: 754 AN XY: 437658

African (AFR) AF: 0.0622 AC: 1242 AN: 19968

American (AMR) AF: 0.00417 AC: 146 AN: 35038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19806

East Asian (EAS) AF: 0.00 AC: 0 AN: 36762

South Asian (SAS) AF: 0.000627 AC: 42 AN: 67006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46906

Middle Eastern (MID) AF: 0.00486 AC: 15 AN: 3086

European-Non Finnish (NFE) AF: 0.0000857 AC: 49 AN: 571712

Other (OTH) AF: 0.00492 AC: 193 AN: 39258

GnomAD4 genome AF: 0.0180 AC: 2705 AN: 149974 Hom.: 67 Cov.: 31 AF XY: 0.0177 AC XY: 1295 AN XY: 73136

African (AFR) AF: 0.0626 AC: 2533 AN: 40448

American (AMR) AF: 0.00743 AC: 111 AN: 14942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.000841 AC: 4 AN: 4758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000310 AC: 21 AN: 67752

Other (OTH) AF: 0.0173 AC: 36 AN: 2078

Alfa AF: 0.00298 Hom.: 9

Bravo AF: 0.0205

Asia WGS AF: 0.00289 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.64
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs73402188; hg19: chr6-31832314;