rs121909178

chr19-17872596-G-Achr19-17872596-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_000453.3(SLC5A5):c.277G>A(p.Gly93Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,572 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G93R) has been classified as Pathogenic.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC5A5 NM_000453.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.35

Genes affected

SLC5A5 (HGNC:11040): (solute carrier family 5 member 5) This gene encodes a member of the sodium glucose cotransporter family. The encoded protein is responsible for the uptake of iodine in tissues such as the thyroid and lactating breast tissue. The iodine taken up by the thyroid is incorporated into the metabolic regulators triiodothyronine (T3) and tetraiodothyronine (T4). Mutations in this gene are associated with thyroid dyshormonogenesis 1.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr19-17872596-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 7668.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.19999588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A5	NM_000453.3	c.277G>A	p.Gly93Ser	missense_variant	1/15	ENST00000222248.4
SLC5A5	XM_011528192.3	c.277G>A	p.Gly93Ser	missense_variant	1/15
SLC5A5	XM_011528193.4	c.10G>A	p.Gly4Ser	missense_variant	2/16
SLC5A5	XM_017027158.2	c.10G>A	p.Gly4Ser	missense_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A5	ENST00000222248.4	c.277G>A	p.Gly93Ser	missense_variant	1/15	1	NM_000453.3	P1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460346 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726588

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74370

Gnomad4 AFR AF: 0.0000241

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: 0.0000658 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	23
Dann	Benign	0.97
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.94	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.15	N
REVEL	Uncertain	0.39
Sift	Benign	0.70	T
Sift4G	Benign	1.0	T
Polyphen		0.12	B
Vest4		0.30
MVP		0.20
MPC		1.8
ClinPred		0.81	D
GERP RS		3.2
Varity_R		0.20
gMVP		0.84

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: rs121909178; hg19: chr19-17983405;