6-166583971-G-T

Position:

• chr6-166583971-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395999.1(RAMACL):​c.*2150C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,128 control chromosomes in the GnomAD database, including 28,948 homozygotes. 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 0.60 (28948 hom., cov: 33)
• Consequence: RAMACL NM_001395999.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

Genes affected

RAMACL (HGNC:21234): (RNA guanine-7 methyltransferase activating subunit like) Predicted to enable RNA binding activity. Predicted to be involved in methylation and recruitment of mRNA capping enzyme to RNA polymerase II holoenzyme complex. Predicted to be part of mRNA cap binding activity complex and mRNA cap methyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

RPS6KA2 (HGNC:10431): (ribosomal protein S6 kinase A2) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains two non-identical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Alternative splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAMACL	NM_001395999.1	c.*2150C>A		3_prime_UTR_variant	1/1	ENST00000444122.3	NP_001382928.1
RPS6KA2	NM_021135.6	c.99+42950C>A		intron_variant		ENST00000265678.9	NP_066958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAMACL	ENST00000444122.3	c.*2150C>A		3_prime_UTR_variant	1/1	6	NM_001395999.1	ENSP00000498060.1
RPS6KA2	ENST00000265678.9	c.99+42950C>A		intron_variant		1	NM_021135.6	ENSP00000265678.4

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90735 AN: 152010 Hom.: 28911 Cov.: 33

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.597 AC: 90829 AN: 152128 Hom.: 28948 Cov.: 33 AF XY: 0.598 AC XY: 44428 AN XY: 74352

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.730

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.553

Alfa AF: 0.486 Hom.: 7784

Bravo AF: 0.616

Asia WGS AF: 0.757 AC: 2634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.11
DANN	Benign	0.47

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: rs3823198; hg19: chr6-166997459;