chr8-117146954-T-G

Variant names:

• chr8-117146954-T-G
• rs144023942
• NM_173851.3:c.72T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173851.3(SLC30A8):​c.72T>G​(p.Ser24Arg) variant causes a missense, splice region 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. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S24S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A8 NM_173851.3 missense, splice_region
• Scores: Splicing: ADA: 0.001279
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733
• Publications: 0 publications found

Genes affected

SLC30A8 (HGNC:20303): (solute carrier family 30 member 8) The protein encoded by this gene is a zinc efflux transporter involved in the accumulation of zinc in intracellular vesicles. This gene is expressed at a high level only in the pancreas, particularly in islets of Langerhans. The encoded protein colocalizes with insulin in the secretory pathway granules of the insulin-secreting INS-1 cells. Allelic variants of this gene exist that confer susceptibility to diabetes mellitus, noninsulin-dependent (NIDDM). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

SLC30A8 Gene-Disease associations (from GenCC):

• type 2 diabetes mellitus

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

LOC105375716 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06690979).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173851.3. 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
	SLC30A8	NM_173851.3	MANE Select	c.72T>G	p.Ser24Arg	missense splice_region	Exon 2 of 8	NP_776250.2	Q8IWU4-1
	SLC30A8	NM_001172811.2		c.-76T>G		splice_region	Exon 4 of 10	NP_001166282.1	Q8IWU4-2
	SLC30A8	NM_001172813.2		c.-76T>G		splice_region	Exon 5 of 11	NP_001166284.1	Q8IWU4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A8	ENST00000456015.7	TSL:1 MANE Select	c.72T>G	p.Ser24Arg	missense splice_region	Exon 2 of 8	ENSP00000415011.2	Q8IWU4-1
	SLC30A8	ENST00000519688.5	TSL:1	c.-76T>G		splice_region	Exon 3 of 9	ENSP00000431069.1	Q8IWU4-2
	SLC30A8	ENST00000521243.5	TSL:1	c.-76T>G		splice_region	Exon 4 of 10	ENSP00000428545.1	Q8IWU4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.5
DANN	Benign	0.96
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.73
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.043
Sift	Benign	0.36	T
Sift4G	Benign	0.18	T
Polyphen		0.0020	B
Vest4		0.22
MutPred		0.23		Gain of MoRF binding (P = 0.0551)
MVP		0.32
MPC		0.050
ClinPred		0.18	T
GERP RS		-4.2
Varity_R		0.067
gMVP		0.22
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0013
dbscSNV1_RF	Benign	0.22
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

Other links and lift over

dbSNP: rs144023942; hg19: chr8-118159193;