3-197950795-G-A

Position:

• chr3-197950795-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000265239.11(IQCG):​c.-59-5109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00784 in 700,918 control chromosomes in the GnomAD database, including 250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (194 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (56 hom.)
• Consequence: IQCG ENST00000265239.11 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.648

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-197950795-G-A is Benign according to our data. Variant chr3-197950795-G-A is described in ClinVar as [Benign]. Clinvar id is 1297422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL35A	NM_000996.4	c.-32-141G>A		intron_variant		ENST00000647248.2	NP_000987.2
IQCG	NM_032263.5	c.-59-5109C>T		intron_variant		ENST00000265239.11	NP_115639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQCG	ENST00000265239.11	c.-59-5109C>T		intron_variant		1	NM_032263.5	ENSP00000265239	P1
RPL35A	ENST00000647248.2	c.-32-141G>A		intron_variant			NM_000996.4	ENSP00000495672	P1

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3842 AN: 151998 Hom.: 192 Cov.: 33

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00879

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0125

GnomAD4 exome AF: 0.00297 AC: 1632 AN: 548802 Hom.: 56 Cov.: 7 AF XY: 0.00243 AC XY: 714 AN XY: 293748

Gnomad4 AFR exome AF: 0.0845

Gnomad4 AMR exome AF: 0.00530

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000257

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000272

Gnomad4 OTH exome AF: 0.00605

GnomAD4 genome AF: 0.0254 AC: 3861 AN: 152116 Hom.: 194 Cov.: 33 AF XY: 0.0242 AC XY: 1796 AN XY: 74358

Gnomad4 AFR AF: 0.0888

Gnomad4 AMR AF: 0.00878

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0120 Hom.: 10

Bravo AF: 0.0290

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs79249954; hg19: chr3-197677666;