NM_000996.4:c.-37T>G

Variant names:

• chr3-197950217-T-G
• rs886058265
• NM_000996.4:c.-37T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000996.4(RPL35A):​c.-37T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,231,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: RPL35A NM_000996.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0250
• Publications: 0 publications found

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]

DRC9 (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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS2: High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000996.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL35A	NM_000996.4	MANE Select	c.-37T>G		5_prime_UTR	Exon 1 of 5	NP_000987.2
	DRC9	NM_032263.5	MANE Select	c.-59-4531A>C		intron	N/A	NP_115639.1	Q9H095-1
	RPL35A	NM_001316311.2		c.-115T>G		5_prime_UTR	Exon 1 of 5	NP_001303240.1	P18077

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL35A	ENST00000647248.2	MANE Select	c.-37T>G		5_prime_UTR	Exon 1 of 5	ENSP00000495672.1	P18077
	RPL35A	ENST00000448864.6	TSL:1	c.-115T>G		5_prime_UTR	Exon 1 of 5	ENSP00000393393.1	P18077
	IQCG	ENST00000265239.11	TSL:1 MANE Select	c.-59-4531A>C		intron	N/A	ENSP00000265239.6	Q9H095-1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000232 AC: 25 AN: 1079058 Hom.: 0 Cov.: 30 AF XY: 0.0000236 AC XY: 12 AN XY: 509366

African (AFR) AF: 0.00 AC: 0 AN: 22964

American (AMR) AF: 0.00 AC: 0 AN: 8408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14384

East Asian (EAS) AF: 0.00 AC: 0 AN: 26510

South Asian (SAS) AF: 0.000983 AC: 19 AN: 19320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2910

European-Non Finnish (NFE) AF: 0.00000217 AC: 2 AN: 919842

Other (OTH) AF: 0.0000916 AC: 4 AN: 43654

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152266 Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Diamond-Blackfan anemia 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		0.025
PromoterAI		-0.044	Neutral
Mutation Taster		=298/2	polymorphism

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

Other links and lift over

dbSNP: rs886058265; hg19: chr3-197677088;