1-44721787-G-T

Position:

• chr1-44721787-G-T

Variant summary

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

The NM_001145636.2(ARMH1):​c.725-2335G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARMH1 NM_001145636.2 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.484

Genes affected

ARMH1 (HGNC:34345): (armadillo like helical domain containing 1)

RNU5F-1 (HGNC:10216): (RNA, U5F small nuclear 1)

LOC105378690 (HGNC:):

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=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMH1	NM_001145636.2	c.725-2335G>T		intron_variant		ENST00000535358.6	NP_001139108.1
RNU5F-1	NR_002753.5	n.115C>A		non_coding_transcript_exon_variant	1/1
LOC105378690	XR_007066059.1	n.166+172C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMH1	ENST00000535358.6	c.725-2335G>T		intron_variant		5	NM_001145636.2	ENSP00000440524	P1
RNU5F-1	ENST00000362507.1	n.116C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

RNU5F-1-associated neurodevelopmental disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

literature only

Institute of Human Genetics, University of Leipzig Medical Center

Oct 09, 2024

This variant was identified as de novo -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.039
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: rs191460263; hg19: chr1-45187459;