chr6-31864537-G-A

Position:

• chr6-31864537-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC44A4	NM_025257.3	c.2011+115C>T		intron_variant		ENST00000229729.11	NP_079533.2
SLC44A4	NM_001178044.2	c.1885+115C>T		intron_variant			NP_001171515.1
SLC44A4	NM_001178045.2	c.1783+115C>T		intron_variant			NP_001171516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC44A4	ENST00000229729.11	c.2011+115C>T		intron_variant		1	NM_025257.3	ENSP00000229729	P1
SLC44A4	ENST00000375562.8	c.1885+115C>T		intron_variant		2		ENSP00000364712
SLC44A4	ENST00000544672.5	c.1783+115C>T		intron_variant		2		ENSP00000444109
SLC44A4	ENST00000487680.1	n.144C>T		non_coding_transcript_exon_variant	1/2	3

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

Gnomad4 AFR exome AF: 0.0622

Gnomad4 AMR exome AF: 0.00417

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000627

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000857

Gnomad4 OTH exome AF: 0.00492

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

Gnomad4 AFR AF: 0.0626

Gnomad4 AMR AF: 0.00743

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000841

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000310

Gnomad4 OTH AF: 0.0173

Alfa AF: 0.00134 Hom.: 4

Bravo AF: 0.0205

Asia WGS AF: 0.00289 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs73402188; hg19: chr6-31832314;