ENST00000449319.2:c.418C>T

Variant names:

• chr11-65573479-C-T
• rs374813667
• ENST00000449319.2:c.418C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000449319.2(FAM89B):​c.418C>T​(p.Leu140Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: FAM89B ENST00000449319.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15
• Publications: 1 publications found

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]

ZNRD2-DT (HGNC:27384): (ZNRD2 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034820765).
• BP6: Variant 11-65573479-C-T is Benign according to our data. Variant chr11-65573479-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3092697.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000449319.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM89B	NM_001098785.2	MANE Select	c.408C>T	p.Ser136Ser	synonymous	Exon 2 of 2	NP_001092255.1	Q8N5H3-3
	FAM89B	NM_001098784.2		c.418C>T	p.Leu140Phe	missense	Exon 2 of 2	NP_001092254.1	Q8N5H3-4
	FAM89B	NM_152832.3		c.369C>T	p.Ser123Ser	synonymous	Exon 2 of 2	NP_690045.1	Q8N5H3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM89B	ENST00000449319.2	TSL:1	c.418C>T	p.Leu140Phe	missense	Exon 2 of 2	ENSP00000402439.2	Q8N5H3-4
	FAM89B	ENST00000530349.2	TSL:2 MANE Select	c.408C>T	p.Ser136Ser	synonymous	Exon 2 of 2	ENSP00000431459.1	Q8N5H3-3
	FAM89B	ENST00000316409.2	TSL:1	c.369C>T	p.Ser123Ser	synonymous	Exon 2 of 2	ENSP00000314829.2	Q8N5H3-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 250922 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461820 Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	11
DANN	Uncertain	0.99
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.1
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.059
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.15	T
Vest4		0.13
MVP		0.014
ClinPred		0.035	T
GERP RS		-1.6
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs374813667; hg19: chr11-65340950;