7-77696894-T-A

Position:

• chr7-77696894-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198467.3(RSBN1L):​c.425T>A​(p.Leu142His) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSBN1L NM_198467.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71

Genes affected

RSBN1L (HGNC:24765): (round spermatid basic protein 1 like) Predicted to enable dioxygenase activity and metal ion binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

APTR (HGNC:44173): (Alu-mediated CDKN1A/p21 transcriptional regulator)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09358391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSBN1L	NM_198467.3	c.425T>A	p.Leu142His	missense_variant	1/8	ENST00000334955.13	NP_940869.2
APTR	NR_038361.1	n.452A>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSBN1L	ENST00000334955.13	c.425T>A	p.Leu142His	missense_variant	1/8	1	NM_198467.3	ENSP00000334040.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.425T>A (p.L142H) alteration is located in exon 1 (coding exon 1) of the RSBN1L gene. This alteration results from a T to A substitution at nucleotide position 425, causing the leucine (L) at amino acid position 142 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.018
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.050	T
Polyphen		0.0020	B
Vest4		0.33
MutPred		0.15		Loss of stability (P = 0.0947);
MVP		0.043
MPC		0.80
ClinPred		0.28	T
GERP RS		0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-77326211;