Genetic Variant SLC44A4:p.Pro684_Tyr685insAsnGlySerLeuAspArgPro (chr6-31863707-A-AGGGCCGGTCCAGGGAGCCGTT) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2

The NM_025257.3(SLC44A4):c.2032_2052dupAACGGCTCCCTGGACCGGCCC(p.Pro684_Tyr685insAsnGlySerLeuAspArgPro) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,612,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SLC44A4
NM_025257.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.66

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_025257.3.

BS2

High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC44A4	NM_025257.3 link	c.2032_2052dupAACGGCTCCCTGGACCGGCCC	p.Pro684_Tyr685insAsnGlySerLeuAspArgPro	conservative_inframe_insertion	Exon 21 of 21	ENST00000229729.11	NP_079533.2	Q53GD3-1A0A140VJH4
SLC44A4	NM_001178044.2 link	c.1906_1926dupAACGGCTCCCTGGACCGGCCC	p.Pro642_Tyr643insAsnGlySerLeuAspArgPro	conservative_inframe_insertion	Exon 20 of 20		NP_001171515.1	Q53GD3-4
SLC44A4	NM_001178045.2 link	c.1804_1824dupAACGGCTCCCTGGACCGGCCC	p.Pro608_Tyr609insAsnGlySerLeuAspArgPro	conservative_inframe_insertion	Exon 21 of 21		NP_001171516.1	Q53GD3-3A0A1U9X8K7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC44A4	ENST00000229729.11 link	c.2032_2052dupAACGGCTCCCTGGACCGGCCC	p.Pro684_Tyr685insAsnGlySerLeuAspArgPro	conservative_inframe_insertion	Exon 21 of 21	1	NM_025257.3	ENSP00000229729.6	Q53GD3-1
SLC44A4	ENST00000375562.8 link	c.1906_1926dupAACGGCTCCCTGGACCGGCCC	p.Pro642_Tyr643insAsnGlySerLeuAspArgPro	conservative_inframe_insertion	Exon 20 of 20	2		ENSP00000364712.4	Q53GD3-4
SLC44A4	ENST00000544672.5 link	c.1804_1824dupAACGGCTCCCTGGACCGGCCC	p.Pro608_Tyr609insAsnGlySerLeuAspArgPro	conservative_inframe_insertion	Exon 21 of 21	2		ENSP00000444109.1	Q53GD3-3
SLC44A4	ENST00000487680.1 link	n.241_261dupAACGGCTCCCTGGACCGGCCC		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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

GnomAD3 exomes

AF:

0.00000818

AC:

AN:

244568

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133548

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000917

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1460430

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726524

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151988

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000612

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Dec 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.2032_2052dup, results in the insertion of 7 amino acid(s) of the SLC44A4 protein (p.Asn678_Pro684dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs755752282, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SLC44A4-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over