rs1244480532

Variant names:

• chr10-96547972-C-G
• rs1244480532
• NM_020123.4:c.977G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-96547972-C-G
• chr10-96547972-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4 BS2

The NM_020123.4(TM9SF3):​c.977G>C​(p.Ser326Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,455,602 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S326N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TM9SF3 NM_020123.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.78
• Publications: 0 publications found

Genes affected

TM9SF3 (HGNC:21529): (transmembrane 9 superfamily member 3) Predicted to be involved in protein localization to membrane. Predicted to be located in exocytic vesicle. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38167518).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM9SF3	NM_020123.4	c.977G>C	p.Ser326Thr	missense_variant	Exon 8 of 15	ENST00000371142.9	NP_064508.3
TM9SF3	XM_011539976.3	c.1031G>C	p.Ser344Thr	missense_variant	Exon 8 of 15		XP_011538278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM9SF3	ENST00000371142.9	c.977G>C	p.Ser326Thr	missense_variant	Exon 8 of 15	1	NM_020123.4	ENSP00000360184.4
TM9SF3	ENST00000490192.1	n.201G>C		non_coding_transcript_exon_variant	Exon 3 of 4	4
TM9SF3	ENST00000649367.1	n.1315G>C		non_coding_transcript_exon_variant	Exon 8 of 15

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1455602 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 723934

African (AFR) AF: 0.00 AC: 0 AN: 33168

American (AMR) AF: 0.00 AC: 0 AN: 43608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25908

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.0000591 AC: 5 AN: 84572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109768

Other (OTH) AF: 0.00 AC: 0 AN: 60124

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Benign	0.46
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.025	N
PhyloP100		7.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.020	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.12	B
Vest4		0.61
MutPred		0.69		Gain of glycosylation at S326 (P = 0.0785);
MVP		0.38
MPC		0.92
ClinPred		0.71	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.85
Mutation Taster		=32/68	disease causing

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: rs1244480532; hg19: chr10-98307729;