3-197950237-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000448864.6(RPL35A):c.-95G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,230,904 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (9 hom.)
• Consequence: RPL35A ENST00000448864.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57

Genes affected

RPL35A (HGNC:10345): (ribosomal protein L35a) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L35AE family of ribosomal proteins. It is located in the cytoplasm. The rat protein has been shown to bind to both initiator and elongator tRNAs, and thus, it is located at the P site, or P and A sites, of the ribosome. Although this gene was originally mapped to chromosome 18, it has been established that it is located at 3q29-qter. Alternative splicing results in multiple transcript variants. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Oct 2015]

IQCG (HGNC:25251): (IQ motif containing G) Enables Hsp70 protein binding activity and calmodulin binding activity. Predicted to be involved in sperm axoneme assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-197950237-G-C is Benign according to our data. Variant chr3-197950237-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 517048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 344 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL35A	NM_000996.4	c.-33+16G>C		intron_variant		ENST00000647248.2
IQCG	NM_032263.5	c.-59-4551C>G		intron_variant		ENST00000265239.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCG	ENST00000265239.11	c.-59-4551C>G		intron_variant		1	NM_032263.5	P1
RPL35A	ENST00000647248.2	c.-33+16G>C		intron_variant			NM_000996.4	P1

Frequencies

GnomAD3 genomes AF: 0.00226 AC: 344 AN: 152228 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00356

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00312 AC: 3366 AN: 1078558 Hom.: 9 Cov.: 30 AF XY: 0.00316 AC XY: 1609 AN XY: 509178

Gnomad4 AFR exome AF: 0.000305

Gnomad4 AMR exome AF: 0.000833

Gnomad4 ASJ exome AF: 0.00396

Gnomad4 EAS exome AF: 0.00253

Gnomad4 SAS exome AF: 0.00152

Gnomad4 FIN exome AF: 0.000619

Gnomad4 NFE exome AF: 0.00330

Gnomad4 OTH exome AF: 0.00341

GnomAD4 genome AF: 0.00228 AC: 348 AN: 152346 Hom.: 2 Cov.: 33 AF XY: 0.00205 AC XY: 153 AN XY: 74516

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00356

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.000957 Hom.: 0

Bravo AF: 0.00220

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	10
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs143337408; hg19: chr3-197677108;