rs759504988

Variant names:

• chr12-12330076-C-A
• NM_018050.4:c.1247G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-12330076-C-A
• chr12-12330076-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018050.4(MANSC1):​c.1247G>T​(p.Arg416Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MANSC1 NM_018050.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

Genes affected

MANSC1 (HGNC:25505): (MANSC domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40911907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANSC1	NM_018050.4	c.1247G>T	p.Arg416Leu	missense_variant	Exon 4 of 4	ENST00000535902.6	NP_060520.2
MANSC1	NM_001363613.2	c.1145G>T	p.Arg382Leu	missense_variant	Exon 5 of 5		NP_001350542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MANSC1	ENST00000535902.6	c.1247G>T	p.Arg416Leu	missense_variant	Exon 4 of 4	1	NM_018050.4	ENSP00000438205.1
MANSC1	ENST00000396349.3	c.1145G>T	p.Arg382Leu	missense_variant	Exon 5 of 5	2		ENSP00000379638.3
MANSC1	ENST00000545735.1	c.1004G>T	p.Arg335Leu	missense_variant	Exon 2 of 2	2		ENSP00000445303.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.56	D
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.32
MutPred		0.77		Loss of disorder (P = 0.0283);.;.;
MVP		0.055
MPC		0.53
ClinPred		0.97	D
GERP RS		3.1
Varity_R		0.22
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-12483010;