1-32221169-C-T

Position:

• chr1-32221169-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019118.5(TMEM234):​c.197G>A​(p.Cys66Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM234 NM_019118.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76

Genes affected

TMEM234 (HGNC:28837): (transmembrane protein 234) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

EIF3I (HGNC:3272): (eukaryotic translation initiation factor 3 subunit I) Contributes to translation initiation factor activity. Involved in translational initiation. Located in extracellular exosome. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Apr 2022]

TMEM234 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM234	NM_019118.5	c.197G>A	p.Cys66Tyr	missense_variant	3/5	ENST00000309777.11	NP_061991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM234	ENST00000309777.11	c.197G>A	p.Cys66Tyr	missense_variant	3/5	1	NM_019118.5	ENSP00000309792.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461456 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726980

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2023

The c.197G>A (p.C66Y) alteration is located in exon 3 (coding exon 3) of the TMEM234 gene. This alteration results from a G to A substitution at nucleotide position 197, causing the cysteine (C) at amino acid position 66 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;.;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.3	M;M;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.6	D;D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.63
MutPred		0.58		Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);
MVP		0.62
MPC		0.81
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.78
gMVP		0.35

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: chr1-32686770;