2-64989955-G-T

Variant names:

• chr2-64989955-G-T
• rs7559202
• NM_003038.5:c.312G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003038.5(SLC1A4):​c.312G>T​(p.Ser104Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S104S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SLC1A4 NM_003038.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 11 publications found

Genes affected

SLC1A4 (HGNC:10942): (solute carrier family 1 member 4) The protein encoded by this gene is a sodium-dependent neutral amino acid transporter for alanine, serine, cysteine, and threonine. Defects in this gene have been associated with developmental delay, microcephaly, and intellectual disability. [provided by RefSeq, Jan 2017]

LINC02245 (HGNC:53134): (long intergenic non-protein coding RNA 2245)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.086 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A4	NM_003038.5	c.312G>T	p.Ser104Ser	synonymous_variant	Exon 1 of 8	ENST00000234256.4	NP_003029.2
SLC1A4	NM_001348406.2	c.-134+1335G>T		intron_variant	Intron 1 of 7		NP_001335335.1
SLC1A4	NM_001348407.2	c.-134+1401G>T		intron_variant	Intron 1 of 7		NP_001335336.1
SLC1A4	NM_001193493.2	c.-134+1335G>T		intron_variant	Intron 1 of 6		NP_001180422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A4	ENST00000234256.4	c.312G>T	p.Ser104Ser	synonymous_variant	Exon 1 of 8	1	NM_003038.5	ENSP00000234256.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 185762 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422314 Hom.: 0 Cov.: 33 AF XY: 0.00000142 AC XY: 1 AN XY: 704130

African (AFR) AF: 0.00 AC: 0 AN: 32712

American (AMR) AF: 0.00 AC: 0 AN: 39626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25506

East Asian (EAS) AF: 0.00 AC: 0 AN: 37570

South Asian (SAS) AF: 0.00 AC: 0 AN: 81720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5480

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092468

Other (OTH) AF: 0.00 AC: 0 AN: 58798

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.1
DANN	Benign	0.88
PhyloP100		0.086
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs7559202; hg19: chr2-65217089;