14-21001079-G-C

Variant names:

• chr14-21001079-G-C
• rs780546065
• NM_014579.4:c.430G>C

Variant summary

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

The NM_014579.4(SLC39A2):​c.430G>C​(p.Ala144Pro) 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. 16/22 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. A144T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC39A2 NM_014579.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 0 publications found

Genes affected

SLC39A2 (HGNC:17127): (solute carrier family 39 member 2) This gene encodes a member of the ZIP family of metal ion transporters. The encoded protein functions as a zinc transporter. Mutations in this gene may be associated with susceptibility to carotid artery disease. Multiple transcript variants have been described. [provided by RefSeq, Mar 2010]

ENSG00000258471 (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=0.05767104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014579.4. 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
	SLC39A2	NM_014579.4	MANE Select	c.430G>C	p.Ala144Pro	missense	Exon 4 of 4	NP_055394.2	Q9NP94-1
	SLC39A2	NM_001256588.2		c.*167G>C		3_prime_UTR	Exon 4 of 4	NP_001243517.1	Q9NP94-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A2	ENST00000298681.5	TSL:1 MANE Select	c.430G>C	p.Ala144Pro	missense	Exon 4 of 4	ENSP00000298681.4	Q9NP94-1
	SLC39A2	ENST00000554422.5	TSL:1	c.*167G>C		3_prime_UTR	Exon 4 of 4	ENSP00000452568.1	Q9NP94-2
	ENSG00000258471	ENST00000647921.1		n.398-1249C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.5
DANN	Benign	0.49
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.18
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.015
Sift	Benign	0.50	T
Sift4G	Benign	0.45	T
Polyphen		0.0030	B
Vest4		0.077
MutPred		0.55		Gain of disorder (P = 0.047)
MVP		0.055
MPC		0.042
ClinPred		0.073	T
GERP RS		0.31
Varity_R		0.060
gMVP		0.36
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs780546065; hg19: chr14-21469238;