11-117181895-G-T

Variant names:

• chr11-117181895-G-T
• rs61729991
• NM_001040455.2:c.394G>T

Variant summary

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

The NM_001040455.2(SIDT2):​c.394G>T​(p.Val132Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V132M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SIDT2 NM_001040455.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.11
• Publications: 0 publications found

Genes affected

SIDT2 (HGNC:24272): (SID1 transmembrane family member 2) Predicted to enable several functions, including AP-1 adaptor complex binding activity; AP-2 adaptor complex binding activity; and RNA transmembrane transporter activity. Involved in RNA transport. Located in lysosomal membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040455.2. 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
	SIDT2	NM_001040455.2	MANE Select	c.394G>T	p.Val132Leu	missense	Exon 3 of 26	NP_001035545.1	Q8NBJ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIDT2	ENST00000324225.9	TSL:1 MANE Select	c.394G>T	p.Val132Leu	missense	Exon 3 of 26	ENSP00000314023.4	Q8NBJ9-1
	SIDT2	ENST00000431081.6	TSL:1	c.394G>T	p.Val132Leu	missense	Exon 3 of 27	ENSP00000399635.2	F5H8L4
	SIDT2	ENST00000524842.5	TSL:3	c.-57G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 9	ENSP00000436983.2	E9PPN9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

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: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0064	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		9.1
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.24
Sift	Benign	0.061	T
Sift4G	Benign	0.072	T
Polyphen		0.10	B
Vest4		0.71
MutPred		0.37		Gain of catalytic residue at V132 (P = 0.0582)
MVP		0.39
MPC		1.0
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.30
gMVP		0.44
Mutation Taster		=48/52	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: rs61729991; hg19: chr11-117052611; COSMIC: COSV54060738; COSMIC: COSV54060738;