rs755719907

Variant names:

• chr12-12330355-G-A
• rs755719907
• NM_018050.4:c.968C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018050.4(MANSC1):​c.968C>T​(p.Thr323Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,886 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (1 hom.)
• Consequence: MANSC1 NM_018050.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.404
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.043842614).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018050.4. 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
	MANSC1	NM_018050.4	MANE Select	c.968C>T	p.Thr323Ile	missense	Exon 4 of 4	NP_060520.2
	MANSC1	NM_001363613.2		c.866C>T	p.Thr289Ile	missense	Exon 5 of 5	NP_001350542.1	Q9H8J5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANSC1	ENST00000535902.6	TSL:1 MANE Select	c.968C>T	p.Thr323Ile	missense	Exon 4 of 4	ENSP00000438205.1	Q9H8J5-1
	MANSC1	ENST00000938078.1		c.968C>T	p.Thr323Ile	missense	Exon 4 of 4	ENSP00000608137.1
	MANSC1	ENST00000938079.1		c.968C>T	p.Thr323Ile	missense	Exon 4 of 4	ENSP00000608138.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251404 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000489

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461886 Hom.: 1 Cov.: 65 AF XY: 0.00000688 AC XY: 5 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.5
DANN	Benign	0.93
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.032	N
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.40
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.0050
Sift	Benign	0.068	T
Sift4G	Benign	0.078	T
Polyphen		0.28	B
Vest4		0.056
MutPred		0.29		Gain of catalytic residue at L328 (P = 0.0214)
MVP		0.014
MPC		0.15
ClinPred		0.018	T
GERP RS		-3.0
Varity_R		0.042
gMVP		0.23
Mutation Taster		=96/4	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: rs755719907; hg19: chr12-12483289;