7-75454840-A-G

Position:

• chr7-75454840-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099415.3(POM121C):​c.-151-13193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 141,216 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.

• Frequency: Genomes: 𝑓 0.0040 (0 hom., cov: 32)
• Consequence: POM121C NM_001099415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

Genes affected

POM121C (HGNC:34005): (POM121 transmembrane nucleoporin C) Predicted to enable nuclear localization sequence binding activity. Predicted to be a structural constituent of nuclear pore. Predicted to be involved in RNA export from nucleus and protein import into nucleus. Predicted to be located in nuclear envelope. Predicted to be part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POM121C	NM_001099415.3	c.-151-13193T>C		intron_variant		ENST00000615331.5
POM121C	NR_160303.1	n.865-8885T>C		intron_variant, non_coding_transcript_variant
POM121C	NR_160304.1	n.846-8885T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POM121C	ENST00000615331.5	c.-151-13193T>C		intron_variant		1	NM_001099415.3	A2
POM121C	ENST00000398379.2	c.-151-13193T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00397 AC: 560 AN: 141130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00159

Gnomad ASJ AF: 0.00746

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000440

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000912

Gnomad OTH AF: 0.00358

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00398 AC: 562 AN: 141216 Hom.: 0 Cov.: 32 AF XY: 0.00397 AC XY: 274 AN XY: 68964

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.00159

Gnomad4 ASJ AF: 0.00746

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000440

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000912

Gnomad4 OTH AF: 0.00354

Alfa AF: 0.000558 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.0
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs2690640; hg19: chr7-75084113; COSMIC: COSV68196311;