11-65573441-C-T

Variant names:

• chr11-65573441-C-T
• ENST00000449319.2:c.380C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001098784.2(FAM89B):​c.380C>T​(p.Pro127Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,088 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM89B NM_001098784.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.77

Genes affected

FAM89B (HGNC:16708): (family with sequence similarity 89 member B) Predicted to enable transcription corepressor binding activity. Predicted to be involved in establishment of cell polarity; negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway; and positive regulation of cell migration. Predicted to be active in cytoplasm and lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

ZNRD2 (HGNC:11328): (zinc ribbon domain containing 2) This antigen is recognized by a subset of anti-centromere antibodies from patients with scleroderma and/or Sjogren's syndrome. Subcellular localization has not yet been established. [provided by RefSeq, Jul 2008]

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 (MetaRNN=0.103114694).
• BP6: Variant 11-65573441-C-T is Benign according to our data. Variant chr11-65573441-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3512535.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM89B	NM_001098785.2	c.370C>T	p.Leu124Leu	synonymous_variant	Exon 2 of 2	ENST00000530349.2	NP_001092255.1
FAM89B	NM_001098784.2	c.380C>T	p.Pro127Leu	missense_variant	Exon 2 of 2		NP_001092254.1
FAM89B	NM_152832.3	c.331C>T	p.Leu111Leu	synonymous_variant	Exon 2 of 2		NP_690045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM89B	ENST00000449319.2	c.380C>T	p.Pro127Leu	missense_variant	Exon 2 of 2	1		ENSP00000402439.2
FAM89B	ENST00000530349.2	c.370C>T	p.Leu124Leu	synonymous_variant	Exon 2 of 2	2	NM_001098785.2	ENSP00000431459.1
FAM89B	ENST00000316409.2	c.331C>T	p.Leu111Leu	synonymous_variant	Exon 2 of 2	1		ENSP00000314829.2
ZNRD2	ENST00000526433.1	c.236C>T	p.Pro79Leu	missense_variant	Exon 3 of 3	3		ENSP00000435982.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461088 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726802

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 10, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	14
DANN	Uncertain	1.0
Eigen	Benign	-0.054
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	0.79	N
REVEL	Benign	0.17
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.012	D
Vest4		0.17
MutPred		0.27		Gain of sheet (P = 0.0061);
MVP		0.081
ClinPred		0.92	D
GERP RS		4.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr11-65340912;