rs782531869

Variant names:

• chr17-28357762-G-A
• NM_152464.3:c.92G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-28357762-G-A
• chr17-28357762-G-C
• chr17-28357762-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_152464.3(TMEM199):​c.92G>A​(p.Arg31Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R31P) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TMEM199 NM_152464.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.66

Genes affected

TMEM199 (HGNC:18085): (transmembrane protein 199) The protein encoded by this gene has been observed to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and coat protein complex I (COPI) in some human cells. The encoded protein shares some homology with the yeast protein Vma12. Defects in this gene are a cause of congenital disorder of glycosylation, type IIp. [provided by RefSeq, Mar 2016]

ENSG00000258924 (HGNC:):

POLDIP2 (HGNC:23781): (DNA polymerase delta interacting protein 2) This gene encodes a protein that interacts with the DNA polymerase delta p50 subunit, as well as with proliferating cell nuclear antigen. The encoded protein maybe play a role in the ability of the replication fork to bypass DNA lesions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr17-28357762-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 218964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.14787018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM199	NM_152464.3	c.92G>A	p.Arg31Gln	missense_variant	Exon 1 of 6	ENST00000292114.8	NP_689677.1
POLDIP2	NM_015584.5	c.-314C>T		upstream_gene_variant		ENST00000540200.6	NP_056399.1
POLDIP2	NM_001290145.2	c.-314C>T		upstream_gene_variant			NP_001277074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM199	ENST00000292114.8	c.92G>A	p.Arg31Gln	missense_variant	Exon 1 of 6	1	NM_152464.3	ENSP00000292114.3
POLDIP2	ENST00000540200.6	c.-314C>T		upstream_gene_variant		1	NM_015584.5	ENSP00000475924.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461204 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726926

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.097
Sift	Benign	0.18	T
Sift4G	Benign	0.13	T
Polyphen		0.51	P
Vest4		0.32
MutPred		0.33		Loss of MoRF binding (P = 0.0326);
MVP		0.20
MPC		0.31
ClinPred		0.46	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.081
gMVP		0.43

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-26684785;