9-100442090-C-G

Variant names:

• chr9-100442090-C-G
• rs139409577
• NM_080655.3:c.152C>G

Variant summary

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

The NM_080655.3(MSANTD3):​c.152C>G​(p.Ala51Gly) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A51V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSANTD3 NM_080655.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81
• Publications: 1 publications found

Genes affected

MSANTD3 (HGNC:23370): (Myb/SANT DNA binding domain containing 3)

MSANTD3-TMEFF1 (HGNC:38838): (MSANTD3-TMEFF1 readthrough) This locus represents naturally occurring read-through transcription from the neighboring MSANTD3 (Myb/SANT-like DNA-binding domain containing 3) and TMEFF1 (transmembrane protein with EGF-like and two follistatin-like domains 1) genes. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Aug 2013]

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=0.006369114).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080655.3. 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
	MSANTD3	NM_080655.3	MANE Select	c.152C>G	p.Ala51Gly	missense	Exon 2 of 3	NP_542386.1	Q96H12-1
	MSANTD3-TMEFF1	NM_001198812.1		c.152C>G	p.Ala51Gly	missense	Exon 1 of 10	NP_001185741.1	Q8IYR6
	MSANTD3	NM_001198805.2		c.152C>G	p.Ala51Gly	missense	Exon 2 of 3	NP_001185734.1	Q96H12-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSANTD3	ENST00000395067.7	TSL:1 MANE Select	c.152C>G	p.Ala51Gly	missense	Exon 2 of 3	ENSP00000378506.2	Q96H12-1
	MSANTD3	ENST00000613183.1	TSL:2	c.152C>G	p.Ala51Gly	missense	Exon 2 of 3	ENSP00000480445.1	Q96H12-1
	MSANTD3	ENST00000622639.4	TSL:3	c.152C>G	p.Ala51Gly	missense	Exon 2 of 3	ENSP00000480622.1	Q96H12-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000567 AC: 14 AN: 247072 AF XY: 0.0000447

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000108

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000137 AC: 20 AN: 1459838 Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7 AN XY: 726230

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.0000225 AC: 1 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86124

European-Finnish (FIN) AF: 0.000344 AC: 18 AN: 52366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111632

Other (OTH) AF: 0.00 AC: 0 AN: 60240

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000824 AC: 10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.034
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0064	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.15
Sift	Benign	0.11	T
Sift4G	Uncertain	0.053	T
Polyphen		0.27	B
Vest4		0.57
MutPred		0.30		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.13
MPC		0.54
ClinPred		0.064	T
GERP RS		5.8
PromoterAI		0.012	Neutral
Varity_R		0.13
gMVP		0.47
Mutation Taster		=62/38	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: rs139409577; hg19: chr9-103204372;