22-32218707-C-T

Variant names:

• chr22-32218707-C-T
• rs201836835
• NM_014227.3:c.1787G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014227.3(SLC5A4):​c.1787G>A​(p.Arg596His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,608 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (1 hom., cov: 31)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: SLC5A4 NM_014227.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.508
• Publications: 0 publications found

Genes affected

SLC5A4 (HGNC:11039): (solute carrier family 5 member 4) Predicted to enable glucose:sodium symporter activity and proton transmembrane transporter activity. Predicted to be involved in sodium ion transport. Predicted to act upstream of or within proton transmembrane transport. Predicted to be active in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC5A4-AS1 (HGNC:53163): (SLC5A4 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016364038).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014227.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A4	NM_014227.3	MANE Select	c.1787G>A	p.Arg596His	missense	Exon 15 of 15	NP_055042.1	Q9NY91
	SLC5A4-AS1	NR_149072.1		n.274+11431C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A4	ENST00000266086.6	TSL:1 MANE Select	c.1787G>A	p.Arg596His	missense	Exon 15 of 15	ENSP00000266086.3	Q9NY91
	SLC5A4-AS1	ENST00000434942.2	TSL:3	n.225-10383C>T		intron	N/A
	SLC5A4-AS1	ENST00000452181.2	TSL:5	n.274+11431C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152040 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251248 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461450 Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15 AN XY: 727046

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.000655 AC: 26 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111666

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152158 Hom.: 1 Cov.: 31 AF XY: 0.0000672 AC XY: 5 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41512

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.84
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.51
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.25
Sift	Benign	0.18	T
Sift4G	Benign	0.39	T
Polyphen		0.0080	B
Vest4		0.14
MVP		0.42
MPC		0.20
ClinPred		0.040	T
GERP RS		-0.46
Varity_R		0.023
gMVP		0.25
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201836835; hg19: chr22-32614694;