chr19-17872596-G-C

Position:

• chr19-17872596-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The ENST00000222248.4(SLC5A5):​c.277G>C​(p.Gly93Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC5A5 ENST00000222248.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• 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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.983
• PP5: Variant 19-17872596-G-C is Pathogenic according to our data. 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A5	NM_000453.3	c.277G>C	p.Gly93Arg	missense_variant	1/15	ENST00000222248.4	NP_000444.1
SLC5A5	XM_011528192.3	c.277G>C	p.Gly93Arg	missense_variant	1/15		XP_011526494.1
SLC5A5	XM_011528193.4	c.10G>C	p.Gly4Arg	missense_variant	2/16		XP_011526495.1
SLC5A5	XM_017027158.2	c.10G>C	p.Gly4Arg	missense_variant	2/16		XP_016882647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A5	ENST00000222248.4	c.277G>C	p.Gly93Arg	missense_variant	1/15	1	NM_000453.3	ENSP00000222248	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Thyroid dyshormonogenesis 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 1998

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.76	D
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	1.0	A
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.78
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.053	T
Polyphen		0.98	D
Vest4		0.80
MutPred		0.95		Gain of MoRF binding (P = 0.0099);
MVP		0.94
MPC		2.0
ClinPred		0.98	D
GERP RS		3.2
Varity_R		0.93
gMVP		0.98

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;