7-141919032-C-A

Variant names:

• chr7-141919032-C-A
• rs781881875
• NM_001001656.3:c.157C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001656.3(OR9A4):​c.157C>A​(p.Arg53Ser) 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. 14/22 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. R53C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR9A4 NM_001001656.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711
• Publications: 1 publications found

Genes affected

OR9A4 (HGNC:15095): (olfactory receptor family 9 subfamily A member 4) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

MGAM (HGNC:7043): (maltase-glucoamylase) This gene encodes maltase-glucoamylase, which is a brush border membrane enzyme that plays a role in the final steps of digestion of starch. The protein has two catalytic sites identical to those of sucrase-isomaltase, but the proteins are only 59% homologous. Both are members of glycosyl hydrolase family 31, which has a variety of substrate specificities. [provided by RefSeq, Jul 2008]

MGAM Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12931946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR9A4	NM_001001656.3	c.157C>A	p.Arg53Ser	missense_variant	Exon 2 of 2	ENST00000641559.1	NP_001001656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR9A4	ENST00000641559.1	c.157C>A	p.Arg53Ser	missense_variant	Exon 2 of 2		NM_001001656.3	ENSP00000493151.1
OR9A4	ENST00000548136.1	c.157C>A	p.Arg53Ser	missense_variant	Exon 1 of 1	6		ENSP00000448789.1
MGAM	ENST00000465654.5	c.-180+11164C>A		intron_variant	Intron 1 of 5	3		ENSP00000419372.1
MGAM	ENST00000497554.1	n.37-10745C>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251344 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.49	.;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.0	L;L
PhyloP100		-0.71
PrimateAI	Benign	0.17	T
PROVEAN	Uncertain	-3.7	.;D
REVEL	Benign	0.038
Sift	Uncertain	0.0050	.;D
Sift4G	Benign	0.063	.;T
Polyphen		0.17	B;B
Vest4		0.12
MutPred		0.45		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.25
MPC		0.11
ClinPred		0.68	D
GERP RS		1.1
PromoterAI		-0.036	Neutral
Varity_R		0.22
gMVP		0.099
Mutation Taster		=100/0	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: rs781881875; hg19: chr7-141618832;