7-77696896-C-T

Position:

• chr7-77696896-C-T

Variant summary

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

The NM_198467.3(RSBN1L):​c.427C>T​(p.Leu143Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RSBN1L NM_198467.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16

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=0.2084974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSBN1L	NM_198467.3	c.427C>T	p.Leu143Phe	missense_variant	1/8	ENST00000334955.13	NP_940869.2
APTR	NR_038361.1	n.450G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSBN1L	ENST00000334955.13	c.427C>T	p.Leu143Phe	missense_variant	1/8	1	NM_198467.3	ENSP00000334040.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1454100 Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 4 AN XY: 723744

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

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

Nov 26, 2024

The c.427C>T (p.L143F) alteration is located in exon 1 (coding exon 1) of the RSBN1L gene. This alteration results from a C to T substitution at nucleotide position 427, causing the leucine (L) at amino acid position 143 to be replaced by a phenylalanine (F). 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	0.073
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.035
Sift	Benign	0.057	T
Sift4G	Benign	0.14	T
Polyphen		0.99	D
Vest4		0.28
MutPred		0.21		Loss of glycosylation at P145 (P = 0.0845);
MVP		0.043
MPC		0.61
ClinPred		0.58	D
GERP RS		2.9
Varity_R		0.086
gMVP		0.15

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: chr7-77326213;