rs781148321

Variant names:

• chr22-21029749-C-A
• NM_004173.3:c.1585G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-21029749-C-A
• chr22-21029749-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004173.3(SLC7A4):​c.1585G>T​(p.Gly529Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. G529R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC7A4 NM_004173.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

Genes affected

SLC7A4 (HGNC:11062): (solute carrier family 7 member 4) Predicted to enable amino acid transmembrane transporter activity. Predicted to be involved in amino acid transport. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291240 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19291633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A4	NM_004173.3	c.1585G>T	p.Gly529Trp	missense_variant	Exon 3 of 5	ENST00000382932.3	NP_004164.2
SLC7A4	XM_047441472.1	c.1585G>T	p.Gly529Trp	missense_variant	Exon 2 of 4		XP_047297428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A4	ENST00000382932.3	c.1585G>T	p.Gly529Trp	missense_variant	Exon 3 of 5	1	NM_004173.3	ENSP00000372390.2
SLC7A4	ENST00000403586.5	c.1585G>T	p.Gly529Trp	missense_variant	Exon 3 of 5	1		ENSP00000384278.1
ENSG00000291240	ENST00000706202.1	n.1585G>T		non_coding_transcript_exon_variant	Exon 3 of 7			ENSP00000516280.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.61
DEOGEN2	Benign	0.019	T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.65	.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.44	N;N
REVEL	Benign	0.22
Sift	Benign	0.055	T;T
Sift4G	Benign	0.062	T;T
Polyphen		0.0030	B;B
Vest4		0.17
MutPred		0.52		Gain of catalytic residue at G529 (P = 0.0182);Gain of catalytic residue at G529 (P = 0.0182);
MVP		0.75
MPC		0.082
ClinPred		0.18	T
GERP RS		2.7
Varity_R		0.053
gMVP		0.66

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-21384038;