12-12330391-G-T

Variant names:

• chr12-12330391-G-T
• rs759881826
• NM_018050.4:c.932C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018050.4(MANSC1):​c.932C>A​(p.Thr311Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MANSC1 NM_018050.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06737286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANSC1	NM_018050.4	c.932C>A	p.Thr311Lys	missense_variant	Exon 4 of 4	ENST00000535902.6	NP_060520.2
MANSC1	NM_001363613.2	c.830C>A	p.Thr277Lys	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.932C>A	p.Thr311Lys	missense_variant	Exon 4 of 4	1	NM_018050.4	ENSP00000438205.1
MANSC1	ENST00000396349.3	c.830C>A	p.Thr277Lys	missense_variant	Exon 5 of 5	2		ENSP00000379638.3
MANSC1	ENST00000545735.1	c.689C>A	p.Thr230Lys	missense_variant	Exon 2 of 2	2		ENSP00000445303.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251414 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 65 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.86
DEOGEN2	Benign	0.0073	T;.;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.083	N
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.067	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	N;.;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.021
Sift	Benign	0.23	T;T;T
Sift4G	Uncertain	0.033	D;D;D
Polyphen		0.0060	B;.;.
Vest4		0.057
MutPred		0.33		Gain of solvent accessibility (P = 0.0021);.;.;
MVP		0.048
MPC		0.11
ClinPred		0.016	T
GERP RS		1.1
Varity_R		0.043
gMVP		0.41

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: rs759881826; hg19: chr12-12483325;