rs149723161

Variant names:

• chr1-26039291-C-A
• rs149723161
• NM_001004434.3:c.988G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-26039291-C-A
• chr1-26039291-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BS2_Supporting

The NM_001004434.3(SLC30A2):​c.988G>T​(p.Ala330Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. A330T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SLC30A2 NM_001004434.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325

Genes affected

SLC30A2 (HGNC:11013): (solute carrier family 30 member 2) The protein encoded by this gene is a zinc transporter that acts as a homodimer. The encoded protein plays a role in secreting zinc into breast milk. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035898954).
• BS2: High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A2	NM_001004434.3	c.988G>T	p.Ala330Ser	missense_variant	Exon 8 of 8	ENST00000374276.4	NP_001004434.1
SLC30A2	NM_032513.5	c.841G>T	p.Ala281Ser	missense_variant	Exon 7 of 7		NP_115902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A2	ENST00000374276.4	c.988G>T	p.Ala330Ser	missense_variant	Exon 8 of 8	1	NM_001004434.3	ENSP00000363394.3
SLC30A2	ENST00000374278.7	c.841G>T	p.Ala281Ser	missense_variant	Exon 7 of 7	1		ENSP00000363396.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461356 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726980

Gnomad4 AFR exome AF: 0.00

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.080	T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.10
Sift	Benign	0.60	T;T
Sift4G	Benign	0.96	T;T
Polyphen		0.0070	B;B
Vest4		0.032
MutPred		0.59		Gain of disorder (P = 0.0295);.;
MVP		0.20
MPC		0.30
ClinPred		0.13	T
GERP RS		3.8
Varity_R		0.067
gMVP		0.42

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: rs149723161; hg19: chr1-26365782;